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Current Research and Scholarly Interests

I am interested in the methodology pertinent to dealing with research problems where biological and behavioral interests meet. These interests have been applied not only in psychiatric research, but in those areas of Cardiology, Pediatrics and other fields of medicine in which behavioral research is becoming ever more salient.

Specifically, I am interested in the methods of assessing the quality of measurement (evaluation of medical tests, reliability, validity), in methods of detecting the sources of errors and correcting them, and in the impacts of such errors both on clinical decision making and on research.

This interest is fundamentally related to my interest in design issues for both valid, powerful and effective research projects. I have been involved in the full range of medical research projects, from randomized clinical trials, to epidemiological studies, to preventions studies and even to basic research projects. From this has come research into the issues of statistical power, and strategies to improve power by exercising design considerations rather than increasing sample size.

Finally I am involved as much as possible with efforts to train medical researchers and clinicians to recognize the problems with inference from research project results.

Abstract

Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment selection for individuals (moderators) and provide early indication of ultimate treatment response (mediators) are needed. The rationale and design of a multi-site, placebo-controlled randomized clinical trial of sertraline examining moderators and mediators of treatment response is described. The target sample is 300 participants with early onset (?30 years) recurrent MDD. Non-responders to an 8-week trial are switched double blind to either bupropion (for sertraline non-responders) or sertraline (for placebo non-responders) for an additional 8 weeks. Clinical moderators include anxious depression, early trauma, gender, melancholic and atypical depression, anger attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression. Biological moderator and mediators include cerebral cortical thickness, task-based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG), cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline and week 1, except DTI, assessed only at baseline. The study is designed to standardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods, and to use advanced data analytic methods to integrate these markers. A Differential Depression Treatment Response Index (DTRI) will be developed. The data, including biological samples (DNA, RNA, and plasma collected before and during treatment), will become available in a public scientific repository.Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC). Identifier: NCT01407094. URL: http://clinicaltrials.gov/show/NCT01407094.

Abstract

Many problems in randomized clinical trial design, execution, analysis, presentation and interpretation stem in part from an inadequate understanding of the roles of moderators and mediators of treatment outcome. As a result, 1) the results of clinical research are slow to have an impact on clinical decision making and thus to benefit patients; 2) it is difficult for clinicians or patients to apply randomized clinical trial results comparing two treatments (treatment versus control); 3) when such trials are conducted at various sites, the results often do not replicate; 4) when the results influence clinical decision making, the results clinicians obtain do not match what researchers report; and 5) the treatment effects comparing treatment and control conditions, particularly for psychiatric treatments, often seem trivial. In this review article, the author reviews and integrates the methodological literature concerning dealing with covariates in trials to emphasize their impact on clinical decision making. The goal of trials should ultimately be to establish who should get the treatment condition rather than the control condition (moderators) and to determine how to obtain the best outcomes with whatever is the preferred treatment (mediators). The author makes recommendations to clinicians as to which trials might best be ignored and which carefully considered, and urges clinical researchers to focus on studies best designed to reduce the burden of mental illness on patients.

Abstract

We found a benefit of citalopram for agitation in the Citalopram for Agitation in Alzheimer's Disease study (CitAD), and wondered if this was mediated by a sedative effect. CitAD was a randomized, placebo-controlled, double-blind, parallel group trial conducted at 8 academic centers in the United States and Canada from August 2009 to January 2013. One hundred sixty-two participants with probable Alzheimer's disease (AD) and clinically significant agitation were analyzed in this study. Participants received a psychosocial intervention and were randomized to receive either citalopram or placebo (approximately half assigned to each group). Participants were rated on the Neurobehavioral Rating Scale Agitation subscale and measures of sedation (i.e., fatigue and somnolence).Using the MacArthur Foundation procedures for documenting a mediator effect, we performed a secondary analysis examining whether sedation mediates the effect of treatment on agitation outcome.We found a statistically significant mediating effect of sedation on agitation outcomes, but the magnitude of the effect was small, only explaining 11% of the variance in agitation, with a significant, but modest effect size of 0.16 (95% CI: 0.08 to 0.22).The benefit of citalopram was partly due to sedation but largely due to other mechanisms of action.

Abstract

High levels of high-frequency heart rate variability (HF-HRV), related to parasympathetic-nervous-system functioning, have been associated with longer survival in patients with myocardial infarction and acute trauma and in patients undergoing palliative care. From animal studies linking higher vagal activity with better immune system functioning and reduced metastases, we hypothesized that higher HF-HRV would predict longer survival in patients with metastatic or recurrent breast cancer (MRBC).Eighty-seven patients with MRBC participated in a laboratory task including a 5-minute resting baseline electrocardiogram. HF-HRV was computed as the natural logarithm of the summed power spectral density of R-R intervals (0.15-0.50 Hz). In this secondary analysis of a study testing whether diurnal cortisol slope predicted survival, we tested the association between resting baseline HF-HRV on survival using Cox proportional hazards models.A total of 50 patients died during a median follow-up of 7.99 years. Higher baseline HF-HRV predicted significantly longer survival, with a hazard ratio of 0.75 (95% confidence interval = 0.60-0.92, p = .006). Visceral metastasis status and baseline heart rate were related to both HF-HRV and survival. However, a combination of HF-HRV and heart rate further improved survival prediction, with a hazard ratio of 0.64 (95% confidence interval = 0.48-0.85, p = .002).Vagal activity of patients with MRBC strongly predicted their survival, extending the known predictive window of HF-HRV in cancer beyond palliative care. Vagal activity can be altered by behavioral, pharmacological, and surgical interventions and may be a promising target for extending life expectancy in patients with metastasizing cancer.

Abstract

To understand the process by which a treatment (T) achieves an effect on outcome (O) and thus to improve the effect of T on O, it is vital to detect mediators, to compare the impact of different mediators, and to develop hypotheses about the causal factors (all mediators) linking T and O. An index is needed to facilitate interpretation of the potential clinical importance of a mediator (M) of choice of T on treatment O in randomized clinical trials (RCTs). Ideally such a mediator effect size should (1) be invariant under any rescaling of M and O consistent with the model used, and (2) reflect the difference between the overall observed effect of T on O and what the maximal effect of T on O could be were the association between T and M broken. A mediator effect size is derived first for the traditional linear model, and then more generally for any categorical (ordered or non-ordered) potential mediator. Issues such as the problem of multiple treatments, outcomes and mediators, and of causal inferences, and the correspondence between this approach and earlier ones, are discussed. Illustrations are given of the application of the approach.

Abstract

Despite depressive disorders being very common there has been little research to guide primary care physicians on the choice of treatment for patients with mild to moderate depression.To evaluate the efficacy of interpersonal counselling compared with selective serotonin reuptake inhibitors (SSRIs), in primary care attenders with major depression and to identify moderators of treatment outcome.A randomised controlled trial in nine centres (DEPICS, Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The primary outcome was remission of the depressive episode (defined as a Hamilton Rating Scale for Depression score ?7 at 2 months). Daily functioning was assessed using the Work and Social Adjustment Scale. Logistic regression models were used to identify moderators of treatment outcome.The percentage of patients who achieved remission at 2 months was significantly higher in the interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P = 0.021). Five moderators of treatment outcome were found: depression severity, functional impairment, anxiety comorbidity, previous depressive episodes and smoking habit.We identified some patient characteristics predicting a differential outcome with pharmacological and psychological interventions. Should our results be confirmed in future studies, these characteristics will help clinicians to define criteria for first-line treatment of depression targeted to patients' characteristics.

The Reliability of Clinical Diagnoses: State of the ArtANNUAL REVIEW OF CLINICAL PSYCHOLOGY, VOL 10Kraemer, H. C.2014; 10: 111-130

Abstract

Reliability of clinical diagnosis is essential for good clinical decision making as well as productive clinical research. The current review emphasizes the distinction between a disorder and a diagnosis and between validity and reliability of diagnoses, and the relationships that exist between them. What is crucial is that reliable diagnoses are essential to establishing valid diagnoses. The present review discusses the theoretical background underlying the evaluation of diagnoses, possible designs of reliability studies, estimation of the reliability coefficient, the standards for assessment of reliability, and strategies for improving reliability without compromising validity.

Abstract

High-intensity interventions are provided to seriously-ill patients in the last months of life by medical sub-specialists. This study was undertaken to determine if doctors' age, ethnicity, medical sub-specialty and personal resuscitation and organ donation preferences influenced their attitudes toward Advance Directives (AD) and to compare a cohort of 2013 doctors to a 1989 (one year before the Patient Self Determination Act in 1990) cohort to determine any changes in attitudes towards AD in the past 23 years.Doctors in two academic medical centers participated in an AD simulation and attitudes survey in 2013 and their responses were compared to a cohort of doctors in 1989.Resuscitation and organ donation preferences (2013 cohort) and attitudes toward AD (1989 and 2013 cohorts).In 2013, 1081 (94.2%) doctors of the 1147 approached participated. Compared to 1989, 2013 cohort did not feel that widespread acceptance of AD would result in less aggressive treatment even of patients who do not have an AD (p<0.001, AUC?=?0.77); had greater confidence in their treatment decisions if guided by an AD (p

Abstract

Identifying treatment moderators may help mental health practitioners arrive at more precise treatment selection for individual patients and can focus clinical research on subpopulations that differ in treatment response.To demonstrate a novel exploratory approach to moderation analysis in randomized clinical trials.A total of 291 adults from a randomized clinical trial that compared an empirically supported psychotherapy with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy as treatments for depression.We selected 8 relatively independent individual moderators out of 32 possible variables. A combined moderator, M*, was developed as a weighted combination of the 8 selected individual moderators. M* was then used to identify individuals for whom psychotherapy may be preferred to SSRI pharmacotherapy or vice versa.Among individual moderators, psychomotor activation had the largest moderator effect size (0.12; 95% CI,?

Abstract

This article describes the clinical utility and feasibility of proposed DSM-5 criteria and measures as tested in the DSM-5 Field Trials in Routine Clinical Practice Settings (RCP). METHODS RCP data were collected online for six months (October 2011 to March 2012). Participants included psychiatrists, licensed clinical psychologists, clinical social workers, advanced practice psychiatric-mental health nurses, licensed counselors, and licensed marriage and family therapists. Clinicians received staged, online training and enrolled at least one patient. Patients completed self-assessments of cross-cutting symptom domains, disability measures, and an evaluation of these measures. Clinicians conducted diagnostic interviews and completed DSM-5 and related assessments and a clinical utility questionnaire.A total of 621 clinicians provided data for 1,269 patients. Large proportions of clinicians reported that the DSM-5 approach was generally very or extremely easy for assessment of both pediatric (51%) and adult (46%) patients and very or extremely useful in routine clinical practice for pediatric (48%) and adult (46%) patients. Clinicians considered the DSM-5 approach to be better (57%) or much better (18%) than that of DSM-IV. Patients, including children age 11 to 17 (47%), parents of children age six to ten (64%), parents of adolescents age 11 to 17 (72%), and adult patients (52%), reported that the cross-cutting measures would help their clinicians better understand their symptoms. Similar patterns in evaluations of feasibility and clinical utility were observed among clinicians from various disciplines.The DSM-5 approach was feasible and clinically useful in a wide range of routine practice settings and favorably received by both clinicians and patients.

Abstract

Objective: Many EEG studies have reported that ADHD is characterized by elevated Theta/Beta ratio (TBR). In this study we conducted a meta-analysis on the TBR in ADHD. Method: TBR data during Eyes Open from location Cz were analyzed from children/adolescents 6-18 years of age with and without ADHD. Results: Nine studies were identified with a total of 1253 children/adolescents with and 517 without ADHD. The grand-mean effect size (ES) for the 6-13 year-olds was 0.75 and for the 6-18 year-olds was 0.62. However the test for heterogeneity remained significant; therefore these ESs are misleading and considered an overestimation. Post-hoc analysis found a decreasing difference in TBR across years, explained by an increasing TBR for the non-ADHD groups. Conclusion: Excessive TBR cannot be considered a reliable diagnostic measure of ADHD, however a substantial sub-group of ADHD patients do deviate on this measure and TBR has prognostic value in this sub-group, warranting its use as a prognostic measure rather than a diagnostic measure.

Abstract

No one treatment is likely to affect all patients with a disorder in the same way. A treatment highly effective for some may be ineffective or even harmful for others. Statistically significant or not, the effect sizes of many treatments tend to be small. Consequently, emphasis in clinical research is gradually shifting (1) to increased focus on effect sizes and (2) to discovery and documentation of moderators of treatment effect on outcome in randomized clinical trials, that is, personalized medicine, in which individual differences between patients are explicitly acknowledged. How to test a null hypothesis of moderation of treatment outcome is reasonably well known. The focus here is on how, under parametric assumptions, to define the strength of moderation, that is, a moderator effect size, either for scientific purposes or for assessment of clinical significance, in order to compare moderators and choose among them and to develop a composite moderator, which might more strongly moderate the effect of a treatment on outcome than any single moderator that might ultimately provide guidance for clinicians as to whom to prescribe what treatment.

Abstract

Objective: This article captures the proceedings of a meeting aimed at defining clinically meaningful effects for use in randomized controlled trials for psychopharmacological agents. Design: Experts from a variety of disciplines defined clinically meaningful effects from their perspectives along with viewpoints about how to design and interpret randomized controlled trials. Setting: The article offers relevant, practical, and sometimes anecdotal information about clinically meaningful effects and how to interpret them. Participants: The concept for this session was the work of co-chairs Richard Keefe and the late Andy Leon. Faculty included Richard Keefe, PhD; James McNulty, AbScB; Robert S. Epstein, MD, MS; Shelby D. Reed, PhD; Juan Sanchez, MD; Ginger Haynes, PhD; Andrew C. Leon, PhD; Helena Chmura Kraemer, PhD; Ellen Frank, PhD, and Kenneth L. Davis, MD. Results: The term clinically meaningful effect is an important aspect of designing and interpreting randomized controlled trials but can be particularly difficult in the setting of psychopharmacology where effect size may be modest, particularly over the short term, because of a strong response to placebo. Payers, regulators, patients, and clinicians have different concerns about clinically meaningful effects and may describe these terms differently. The use of moderators in success rate differences may help better delineate clinically meaningful effects. Conclusion: There is no clear consensus on a single definition for clinically meaningful differences in randomized controlled trials, and investigators must be sensitive to specific concerns of stakeholders in psychopharmacology in order to design and execute appropriate clinical trials.

Abstract

The goal of this mixed-methods study was to characterize the perceptions of multicultural long-term care nurses about patient dignity at the end-of-life (EOL). The study was conducted in a large, urban, long-term care (LTC) facility. Participants were 45 long-term care nurses and 26 terminally ill nursing home residents. Nurses completed an openended interview about their perceptions of the concept of dying with dignity, and the data were analyzed using grounded theory methods. Main themes identified as promoting resident dignity at the EOL included treating them with respect, helping them prepare for the EOL, promoting shared decision-making, and providing high-quality care. The nurses? cultural and religious backgrounds influenced their perceptions of what constitutes dignity-conserving care. Foreign-born nurses stressed the need for EOL rituals, but this was strikingly absent in the statements of U.S.-born nurses. Foreign-born Catholic nurses stated that the dying experience should not be altered using analgesics to relieve suffering or by attempts to hasten death by forgoing curative therapy or by other means. Nurses and terminally ill individuals completed the Dignity Card-sort Tool (DCT). A comparison of the DCT responses of the LTC nurses cohort with those of the terminally ill participants revealed that the nurses felt patient dignity was eroded when patient wishes were not followed and when they were treated without respect. In contrast, dying LTC residents felt that poor medical care and loss of ability to choose care options were the most important factors leading to erosion of dignity.

Abstract

The DSM-5 Field Trials were designed to obtain precise (standard error,0.1) estimates of the intraclass kappa asa measure of the degree to which two clinicians could independently agree on the presence or absence of selected DSM-5 diagnoses when the same patient was interviewed on separate occasions, in clinical settings, and evaluated with usual clinical interview methods.Eleven academic centers in the United States and Canada were selected,and each was assigned several target diagnoses frequently treated in that setting.Consecutive patients visiting a site during the study were screened and stratified on the basis of DSM-IV diagnoses or symptomatic presentations. Patients were randomly assigned to two clinicians for a diagnostic interview; clinicians were blind to any previous diagnosis. All data were entered directly via an Internet-based software system to a secure central server. Detailed research design and statistical methods are presented in an accompanying article.There were a total of 15 adult and eight child/adolescent diagnoses for which adequate sample sizes were obtained to report adequately precise estimates of the intraclass kappa. Overall, five diagnoses were in the very good range(kappa=0.60?0.79), nine in the good range(kappa=0.40?0.59), six in the questionable range (kappa = 0.20?0.39), and three in the unacceptable range (kappa values,0.20). Eight diagnoses had insufficient sample sizes to generate precise kappa estimates at any site.Most diagnoses adequately tested had good to very good reliability with these representative clinical populations assessed with usual clinical interview methods. Some diagnoses that were revised to encompass a broader spectrum of symptom expression or had a more dimensional approach tested in the good to very good range.

Abstract

To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged > 40 years, having psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia, diagnosed using DSM-IV-TR criteria.We used equipoise-stratified randomization (a hybrid of complete randomization and clinician's choice methods) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk. Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters. The study was conducted from October 2005 to October 2010.Primary metabolic markers (body mass index, blood pressure, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), percentage of patients who stay on the randomly assigned atypical antipsychotic for at least 6 months, psychopathology, percentage of patients who develop metabolic syndrome, and percentage of patients who develop serious and nonserious adverse events.Because of a high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different atypical antipsychotics (P < .01), suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events for all atypical antipsychotics in the study.Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients.ClinicalTrials.gov identifier: NCT00245206.

Abstract

The quality of all clinical decision-making, as well as power and precision in clinical research results, depends fundamentally on the quality of the measures used. Yet evaluations of the quality of clinical measures likely to be used either in clinic or research applications are difficult to execute or to critique because the criteria for judging such studies are so ill-defined. Here a set of guidelines is proposed, modeled on CONSORT guidelines for randomized clinical trials, first defining the terms often inconsistently used in the research literature and then identifying certain errors that seem to recur in evaluation studies.

Abstract

This article discusses the design,sampling strategy, implementation,and data analytic processes of the DSM-5 Field Trials.The DSM-5 Field Trials were conducted by using a test-retest reliability design with a stratified sampling approach across six adult and four pediatric sites in the United States and one adult site in Canada. A stratified random sampling approach was used to enhance precision in the estimation of the reliability coefficients. A web-based research electronic data capture system was used for simultaneous data collection from patients and clinicians across sites and for centralized data management.Weighted descriptive analyses, intraclass kappa and intraclass correlation coefficients for stratified samples, and receiver operating curves were computed. The DSM-5 Field Trials capitalized on advances since DSM-III and DSM-IV in statistical measures of reliability (i.e., intraclass kappa for stratified samples) and other recently developed measures to determine confidence intervals around kappa estimates.Diagnostic interviews using DSM-5 criteria were conducted by 279 clinicians of varied disciplines who received training comparable to what would be available to any clinician after publication of DSM-5.Overall, 2,246 patients with various diagnoses and levels of comorbidity were enrolled,of which over 86% were seen for two diagnostic interviews. A range of reliability coefficients were observed for the categorical diagnoses and dimensional measures.Multisite field trials and training comparable to what would be available to any clinician after publication of DSM-5 provided ?real-world? testing of DSM-5 proposed diagnoses.

Abstract

The authors sought to document, in adult and pediatric patient populations, the development, descriptive statistics,and test-retest reliability of cross-cutting symptom measures proposed for inclusion in DSM-5.Data were collected as part of the multisite DSM-5 Field Trials in large academic settings. There were seven sites focusing on adult patients and four sites focusing on child and adolescent patients.Cross-cutting symptom measures were self-completed by the patient or an informant before the test and the retest interviews, which were conducted from 4 hours to 2 weeks apart. Clinician-report measures were completed during or after the clinical diagnostic interviews. Informants included adult patients, child patients age 11 and older, parents of all child patients age 6 and older, and legal guardians for adult patients unable to self-complete the measures. Study patients were sampled in a stratified design,and sampling weights were used in data analyses. The mean scores and standard deviations were computed and pooled across adult and child sites. Reliabilities were reported as pooled intraclass correlation coefficients (ICCs) with 95% confidence intervals.In adults, test-retest reliabilities of the cross-cutting symptom items generally were good to excellent. At the child and adolescent sites, parents were also reliablereporters of their children?s symptoms,with few exceptions. Reliabilities were not as uniformly good for child respondents, and ICCs for several items fell into the questionable range in this age group. Clinicians rated psychosis with good reliability in adult patients but were less reliable in assessing clinical domains related to psychosis in children and to suicide in all age groups.These results show promising test-retest reliability results for this group of assessments, many of which are newly developed or have not been previously tested in psychiatric populations

Abstract

For most of the twentieth century, the focus was on "nature" versus "nurture", i.e. genetic versus environmental effects on disorders. Now it is increasingly recognized that a disorder may reflect genes and environments "working together". A gene may moderate an environmental risk factor, it may be mediated by an environmental risk factor. The environmental risk factor may be proxy to the gene, and the two may be independent risk factors. Which of these situations pertain influences both subsequent research and clinical and policy decision-making. However, recent meta-analyses attempting to confirm the Caspi et al. (Science, 301, 386-389, 2003) hypothesis indicate that the methodological issues relating to establishing specifically a moderating effect of a gene on an environmental factor are not well understood. The discussion here concerns the definition of "moderator", how it is distinct from other ways in which gene and environment can "work together", the methods needed to establish such a moderator, and the public health significance of such efforts.

Abstract

Interest in commonly co-occurring depression and disruptive behavior disorders in children has yielded a small body of research that estimates the prevalence of this comorbid condition and compares children with the comorbid condition and children with depression or disruptive behavior disorders alone with respect to antecedents and outcomes. Prior studies have used one of two different approaches to measure comorbid disorders: (1) meeting criteria for two DSM or ICD diagnoses or (2) scoring .5 SD above the mean or higher on two dimensional scales. This study compares two snapshots of comorbidity taken simultaneously in the same sample with each of the measurement approaches. The Developmental Pathways Project administered structured diagnostic interviews as well as dimensional scales to a community-based sample of 521 11-12 year olds to assess depression and disruptive behavior disorders. Clinical caseness indicators of children identified as "comorbid" by each method were examined concurrently and 3-years later. Cross-classification of adolescents via the two approaches revealed low agreement. When other indicators of caseness, including functional impairment, need for services, and clinical elevations on other symptom scales were examined, adolescents identified as comorbid via dimensional scales only were similar to those who were identified as comorbid via DSM-IV diagnostic criteria. Findings suggest that when relying solely on DSM diagnostic criteria for comorbid depression and disruptive behavior disorders, many adolescents with significant impairment will be overlooked. Findings also suggest that lower dimensional scale thresholds can be set when comorbid conditions, rather than single forms of psychopathology, are being identified.

Abstract

In 1983, reports of antibodies in subjects with major depressive disorder (MDD) to an as-yet uncharacterized infectious agent associated with meningoencephalitis in horses and sheep led to molecular cloning of the genome of a novel, negative-stranded neurotropic virus, Borna disease virus (BDV). This advance has enabled the development of new diagnostic assays, including in situ hybridization, PCR and serology based on recombinant proteins. Since these assays were first implemented in 1990, more than 80 studies have reported an association between BDV and a wide range of human illnesses that include MDD, bipolar disorder (BD), schizophrenia (SZ), anxiety disorder, chronic fatigue syndrome, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme. However, to date there has been no blinded case-control study of the epidemiology of BDV infection. Here, in a United States-based, multi-center, yoked case-control study with standardized methods for clinical assessment and blinded serological and molecular analysis, we report the absence of association of psychiatric illness with antibodies to BDV or with BDV nucleic acids in serially collected serum and white blood cell samples from 396 subjects, a study population comprised of 198 matched pairs of patients and healthy controls (52 SZ/control pairs, 66 BD/control pairs and 80 MDD/control pairs). Our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders.

Abstract

One aim of personalized medicine is to determine which treatment is to be preferred for an individual patient, given all patient information available. Particularly in mental health, however, there is a lack of a single objective, reliable measure of outcome that is sensitive to crucial individual differences among patients.We examined the feasibility of quantifying the total clinical value provided by a treatment (measured by both harms and benefits) in a single metric. An expert panel was asked to compare 100 pairs of patients, one from each treatment group, who had participated in a randomized clinical trial (RCT) involving interpersonal psychotherapy (IPT) and escitalopram, selecting the patient with the preferred outcome considering both benefits and harms.From these results, an integrated preference score (IPS) was derived, such that the differences between any two patients' IPSs would predict the clinicians' preferences. This IPS was then computed for all patients in the RCT. A second set of 100 pairs was rated by the panel. Their preferences were highly correlated with the IPS differences (r=0.84). Finally, the IPS was used as the outcome measure comparing IPT and escitalopram. The 95% confidence interval (CI) for the effect size comparing treatments indicated clinical equivalence of the treatments.A metric that combines benefits and harms of treatments could increase the value of RCTs by making clearer which treatments are preferable and, ultimately, for whom. Such methods result in more precise estimation of effect sizes, without increasing the required sample size.

Abstract

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Abstract

Few of the limited randomized controlled trails (RCTs) for adolescent anorexia nervosa (AN) have explored the effects of moderators and mediators on outcome. This study aimed to identify treatment moderators and mediators of remission at end of treatment (EOT) and 6- and 12-month follow-up (FU) for adolescents with AN (N = 121) who participated in a multi-center RCT of family-based treatment (FBT) and individual adolescent focused therapy (AFT). Mixed effects modeling were utilized and included all available outcome data at all time points. Remission was defined as ? 95% IBW plus within 1 SD of the Eating Disorder Examination (EDE) norms. Eating related obsessionality (Yale-Brown-Cornell Eating Disorder Total Scale) and eating disorder specific psychopathology (EDE-Global) emerged as moderators at EOT. Subjects with higher baseline scores on these measures benefited more from FBT than AFT. AN type emerged as a moderator at FU with binge-eating/purging type responding less well than restricting type. No mediators of treatment outcome were identified. Prior hospitalization, older age and duration of illness were identified as non-specific predictors of outcome. Taken together, these results indicate that patients with more severe eating related psychopathology have better outcomes in a behaviorally targeted family treatment (FBT) than an individually focused approach (AFT).

Another Point of View: Superiority, Noninferiority, and the Role of Active ComparatorsJOURNAL OF CLINICAL PSYCHIATRYKraemer, H. C.2011; 72 (10): 1350-1352

Abstract

Despite substantial agreement with points made by Andrew C. Leon, PhD, in his article, I am not in complete agreement in a few areas. The definition of noninferiority proposed by Leon allows drugs somewhat less effective than placebo to be characterized as noninferior to placebo, and 2 active drugs may each be simultaneously noninferior to the other. Moreover, including a placebo arm in comparing 2 active drugs is of no use in deciding whether the study is well designed or not, since a significant difference between one of the active arms and the placebo may be due to chance or to a bias in the design. An alternative view of the situation is presented.

Abstract

Numerous longitudinal studies have identified risk factors for the onset of most eating disorders (EDs). Identifying women at highest risk within a high-risk sample would allow for focusing of preventive resources and also suggests different etiologies.A longitudinal cohort study over 3 years in a high-risk sample of 236 college-age women randomized to the control group of a prevention trial for EDs. Potential risk factors and interactions between risk factors were assessed using the methods developed previously. Main outcome measures were time to onset of a subthreshold or full ED.At the 3-year follow-up, 11.2% of participants had developed a full or partial ED. Seven of 88 potential risk factors could be classified as independent risk factors, seven as proxies, and two as overlapping factors. Critical comments about eating from teacher/coach/siblings and a history of depression were the most potent risk factors. The incidence for participants with either or both of these risk factors was 34.8% (16/46) compared to 4.2% (6/144) for participants without these risk factors, with a sensitivity of 0.75 and a specificity of 0.82.Targeting preventive interventions at women with high weight and shape concerns, a history of critical comments about eating weight and shape, and a history of depression may reduce the risk for EDs.

Abstract

To compare health-care utilization between participants who met DSM-IV criteria for binge eating disorder (BED) and those engaged in recurrent binge eating (RBE) and to evaluate whether objective binge eating (OBE) days, a key measurement for diagnosing BED, predicted health-care costs.We obtained utilization and cost data from electronic medical records to augment patient reported data for 100 adult female members of a large health maintenance organization who were enrolled in a randomized clinical trial to treat binge eating.Total costs did not differ between the BED and RBE groups (? = -0.117, z = -0.48, p = .629), nor did the number of OBE days predict total costs (? = -0.017, z = -1.01, p = .313).Findings suggest that the medical impairment, as assessed through health care costs, caused by BED may not be greater than impairment caused by RBE. The current threshold number of two OBE days/week as a criterion for BED may need to be reconsidered.

How to assess the clinical impact of treatments on patients, rather than the statistical impact of treatments on measuresINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCHKraemer, H. C., Frank, E., Kupfer, D. J.2011; 20 (2): 63-72

Abstract

While randomized clinical trials (RCTs) should provide the basis for evidence-based medicine, as currently designed and analyzed, they often mislead clinical decision-making. Comparative effectiveness evaluation of two treatments [Treatment 1 (T1) versus Treatment 2 (T2)] should not be determined by the statistical effect of treatments on individual measures of outcome (benefits and/or harms), but rather on the clinical effects of treatments on individual patients who can experience both benefits and harms. Such strategies for evaluation require both methods for statistical assessment of the rates of co-occurrence of such benefits and harms, and clinical assessment of their combined clinical impact on patients. The strategies discussed here are possible solutions to this dilemma. It is crucial to develop successful strategies to assess the effects of treatments on individual patients.

Abstract

Pilot studies represent a fundamental phase of the research process. The purpose of conducting a pilot study is to examine the feasibility of an approach that is intended to be used in a larger scale study. The roles and limitations of pilot studies are described here using a clinical trial as an example. A pilot study can be used to evaluate the feasibility of recruitment, randomization, retention, assessment procedures, new methods, and implementation of the novel intervention. A pilot study is not a hypothesis testing study. Safety, efficacy and effectiveness are not evaluated in a pilot. Contrary to tradition, a pilot study does not provide a meaningful effect size estimate for planning subsequent studies due to the imprecision inherent in data from small samples. Feasibility results do not necessarily generalize beyond the inclusion and exclusion criteria of the pilot design. A pilot study is a requisite initial step in exploring a novel intervention or an innovative application of an intervention. Pilot results can inform feasibility and identify modifications needed in the design of a larger, ensuing hypothesis testing study. Investigators should be forthright in stating these objectives of a pilot study. Grant reviewers and other stakeholders should expect no more.

Abstract

This study compared the best available treatment for bulimia nervosa, cognitive-behavioural therapy (CBT) augmented by fluoxetine if indicated, with a stepped-care treatment approach in order to enhance treatment effectiveness.To establish the relative effectiveness of these two approaches.This was a randomised trial conducted at four clinical centres (Clinicaltrials.gov registration number: NCT00733525). A total of 293 participants with bulimia nervosa were randomised to one of two treatment conditions: manual-based CBT delivered in an individual therapy format involving 20 sessions over 18 weeks and participants who were predicted to be non-responders after 6 sessions of CBT had fluoxetine added to treatment; or a stepped-care approach that began with supervised self-help, with the addition of fluoxetine in participants who were predicted to be non-responders after six sessions, followed by CBT for those who failed to achieve abstinence with self-help and medication management.Both in the intent-to-treat and completer samples, there were no differences between the two treatment conditions in inducing recovery (no binge eating or purging behaviours for 28 days) or remission (no longer meeting DSM-IV criteria). At the end of 1-year follow-up, the stepped-care condition was significantly superior to CBT.Therapist-assisted self-help was an effective first-level treatment in the stepped-care sequence, and the full sequence was more effective than CBT suggesting that treatment is enhanced with a more individualised approach.

Abstract

The aim of this study was to replicate and extend results of a previous blended efficacy and effectiveness trial of a low-intensity, manual-based guided self-help form of cognitive-behavioral therapy (CBT-GSH) for the treatment of binge eating disorders in a large health maintenance organization (HMO) and to compare them with usual care.To extend previous findings, the investigators modified earlier recruitment and assessment approaches and conducted a randomized clinical trial to better reflect procedures that may be reasonably carried out in real-world practices. The intervention was delivered by master's-level interventionists to 160 female members of a health maintenance organization who met diagnostic criteria for recurrent binge eating. Data collected at baseline, immediately posttreatment, and at six- and 12-month follow-ups were used in intent-to-treat analyses.At the 12-month follow-up, CBT-GSH resulted in greater remission from binge eating (35%, N=26) than usual care (14%, N=10) (number needed to treat=5). The CBT-GSH group also demonstrated greater improvements in dietary restraint (d=.71) and eating, shape, and weight concerns (d=1.10, 1.24, and .98, respectively) but not weight change.Replication of the pattern of previous findings suggests that CBT-GSH is a robust treatment for patients with recurrent binge eating. The magnitude of changes was significantly smaller than in the original study, however, suggesting that patients recruited and assessed with less intensive procedures may respond differently from their counterparts enrolled in trials requiring more comprehensive procedures.

Abstract

Numerous studies have examined the comorbidity of depression with cancer, and some have indicated that depression may be associated with cancer progression or survival. However, few studies have assessed whether changes in depression symptoms are associated with survival.In a secondary analysis of a randomized trial of supportive-expressive group therapy, 125 women with metastatic breast cancer (MBC) completed a depression symptom measure (Center for Epidemiologic Studies-Depression Scale [CES-D]) at baseline and were randomly assigned to a treatment group or to a control group that received educational materials. At baseline and three follow-up points, 101 of 125 women completed a depression symptom measure. We used these data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms over the first year of the study (the length of the intervention) would be associated with longer survival.Median survival time was 53.6 months for women with decreasing CES-D scores over 1 year and 25.1 months for women with increasing CES-D scores. There was a significant effect of change in CES-D over the first year on survival out to 14 years (P = .007) but no significant interaction between treatment condition and CES-D change on survival. Neither demographic nor medical variables explained this association.Decreasing depression symptoms over the first year were associated with longer subsequent survival for women with MBC in this sample. Further research is necessary to confirm this hypothesis in other samples, and causation cannot be assumed based on this analysis.

Abstract

Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy.A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks.Participants with higher scores on the need for medical reassurance factor of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission.This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Abstract

At the 2008 annual meeting of the American College of Neuropsychopharmacology (ACNP), a symposium was devoted to the following question: 'what have we learned about the design of pragmatic clinical trials (PCTs) from the recent costly long-term, large-scale trials of psychiatric treatments?' in order to inform the design of future trials. In all, 10 recommendations were generated placing emphasis on (1) appropriate conduct of pragmatic trials; (2) clinical, rather than, merely statistical significance; (3) sampling from the population clinicians are called upon to treat; (4) clinical outcomes of patients, rather than, on outcome measures; (5) use of stratification, controlling, or adjusting when necessary and not otherwise; (6) appropriate consideration of site differences in multisite studies; (7) encouragement of 'post hoc' exploration to generate (not test) hypotheses; (8) precise articulation of the treatment strategy to be tested and use of the corresponding appropriate design; (9) expanded opportunity for training of researchers and reviewers in RCT principles; and (10) greater emphasis on data sharing.

Abstract

To determine whether late-onset schizophrenia (LOS, onset after age 40) should be considered a distinct subtype of schizophrenia.Participants included 359 normal comparison subjects (NCs) and 854 schizophrenia out-patients age >40 (110 LOS, 744 early-onset schizophrenia or EOS). Assessments included standardized measures of psychopathology, neurocognition, and functioning.Early-onset schizophrenia and LOS groups differed from NCs on all measures of psychopathology and functioning, and most cognitive tests. Early-onset schizophrenia and LOS groups had similar education, severity of depressive, negative, and deficit symptoms, crystallized knowledge, and auditory working memory, but LOS patients included more women and married individuals, had less severe positive symptoms and general psychopathology, and better processing speed, abstraction, verbal memory, and everyday functioning, and were on lower antipsychotic doses. Most EOS-LOS differences remained significant after adjusting for age, gender, severity of negative or deficit symptoms, and duration of illness.Late-onset schizophrenia should be considered a subtype of schizophrenia.

Abstract

Wisdom has received increasing attention in empirical research in recent years, especially in gerontology and psychology, but consistent definitions of wisdom remain elusive. We sought to better characterize this concept via an expert consensus panel using a 2-phase Delphi method.A survey questionnaire comprised 53 Likert scale statements related to the concepts of wisdom, intelligence, and spirituality was developed to determine if and how wisdom was viewed as being distinct from the latter 2 concepts. Of the 57 international wisdom experts contacted by e-mail, 30 completed the Phase 1 survey and 27 also completed the Phase 2 survey.In Phase 1, there were significant group differences among the concepts of wisdom, intelligence, and spirituality on 49 of the 53 items rated by the experts. Wisdom differed from intelligence on 46 of these 49 items, whereas wisdom differed from spirituality on 31 items. In Phase 2, we sought to define wisdom further by selecting 12 items based on Phase 1 results. Most experts agreed on many of the suggested characteristics of wisdom-that is, it is uniquely human; a form of advanced cognitive and emotional development that is experience driven; and a personal quality, albeit a rare one, which can be learned, increases with age, can be measured, and is not likely to be enhanced by taking medication.There was considerable agreement among the expert participants on wisdom being a distinct entity and a number of its characteristic qualities. These data should help in designing additional empirical research on wisdom.

Abstract

Metabolic syndrome (MetS) is prevalent among antipsychotic-treated patients; however, in psychiatric clinics, scarce resources often limit the feasibility of monitoring all 5 criteria that are necessary for diagnosing MetS. As one goal of the MetS definition is to facilitate the clinical identification of insulin-resistant individuals, other biomarkers of insulin resistance have been explored. However, there are relatively few data from antipsychotic-treated patients, especially on the association between these markers and the clinical MetS diagnosis.We analyzed data from 196 psychiatric patients over age 40 years enrolled in an ongoing study of antipsychotic-related metabolic effects that began in August 2005. In addition to anthropometric measures and MetS criteria, levels of certain metabolism-related peptides (ghrelin, adiponectin, peptide YY, leptin, and insulin) were measured. The utility of these clinical and metabolic markers to identify individuals with MetS was evaluated by constructing receiver operating characteristic curves. Optimal cutoff values were calculated for markers with the greatest area under the curve on the basis of sensitivities and specificities for MetS diagnosis.Ninety-nine subjects (50.5%) met MetS criteria. The receiver operating characteristic analysis found that waist circumference, triglyceride to high-density lipoprotein (TG:HDL) ratio, and body mass index had the greatest area under the curve. The waist circumference cutoff value of 40 inches, TG:HDL ratio of 2.6, and body mass index of 28 kg/m² yielded sensitivities and specificities of 73% and 80%, 74% and 78%, and 75% and 74%, respectively, for MetS diagnosis.Waist circumference, TG:HDL cholesterol ratio, or body mass index could be used as screens for identifying possible MetS in antipsychotic-treated patients to prompt complete investigation into all MetS criteria.clinicaltrials.gov Identifier: NCT00245206.

Abstract

The relationship between aging and practice effects on longitudinal neuropsychological assessments was investigated in middle-aged and older people with schizophrenia and healthy controls.Older people with schizophrenia (n = 107; M age = 56.1) and age-comparable nonpsychiatric controls (n = 107; M age = 57.7) were scheduled to receive annual assessments on a comprehensive battery of neuropsychological tests for an average of 2.5 years (range 11 months to 4 years). Mixed-model analyses were used to separately examine the effects of practice and age on test performance.Number of prior assessments (practice) was associated with significant performance improvement across assessments, whereas older age was associated with significant decline in performance. The groups did not differ significantly in extent of age-related cognitive decline, but a three-way interaction among group, age, and practice was found, such that greater age-related decline in practice effects were found for older people with schizophrenia relative to nonpsychiatric participants.This study did not find any evidence of neurodegenerative age-related decline in neuropsychological abilities in middle-aged and older people with schizophrenia, but older age was associated with diminished ability to benefit from repeated exposure to cognitive tasks in people with schizophrenia. Cognitive impairment in schizophrenia may combine with cognitive decline associated with normal aging to reduce practice effects in older patients. These findings have important implications for the design of studies examining the longitudinal trajectory of cognitive functioning across the life span of people with schizophrenia, as well as clinical trials that attempt to demonstrate cognitive enhancement in these individuals.

Abstract

Adoption of effective treatments for recurrent binge-eating disorders depends on the balance of costs and benefits. Using data from a recent randomized controlled trial, we conducted an incremental cost-effectiveness analysis (CEA) of a cognitive-behavioral therapy guided self-help intervention (CBT-GSH) to treat recurrent binge eating compared to treatment as usual (TAU).Participants were 123 adult members of an HMO (mean age = 37.2 years, 91.9% female, 96.7% non-Hispanic White) who met criteria for eating disorders involving binge eating as measured by the Eating Disorder Examination (C. G. Fairburn & Z. Cooper, 1993). Participants were randomized either to treatment as usual (TAU) or to TAU plus CBT-GSH. The clinical outcomes were binge-free days and quality-adjusted life years (QALYs); total societal cost was estimated using costs to patients and the health plan and related costs.Compared to those receiving TAU only, those who received TAU plus CBT-GSH experienced 25.2 more binge-free days and had lower total societal costs of $427 over 12 months following the intervention (incremental CEA ratio of -$20.23 per binge-free day or -$26,847 per QALY). Lower costs in the TAU plus CBT-GSH group were due to reduced use of TAU services in that group, resulting in lower net costs for the TAU plus CBT group despite the additional cost of CBT-GSH.Findings support CBT-GSH dissemination for recurrent binge-eating treatment.

Abstract

To examine the operating characteristics of the Patient Health Questionnaire eating disorder module (PHQ-ED) for identifying bulimia nervosa/binge eating disorder (BN/BED) or recurrent binge eating (RBE) in a community sample and to compare true positive (TP) versus false positive (FP) cases on clinical validators.Two hundred and fifty-nine screen-positive individuals and a random sample of 89 screen negative cases completed a diagnostic interview. Sensitivity, specificity, and positive predictive value (PPV) were calculated. TP and FP cases were compared using t-tests and Chi-square tests.The PHQ-ED had high sensitivity (100%) and specificity (92%) for detecting BN/BED or RBE, but PPV was low (10 or 19%). TP and FP cases did not differ significantly on frequency of subjective bulimic episodes, objective overeating, restraint, on BMI, and on self-rated health.The PHQ-ED is recommended for use in large populations only in conjunction with follow-up questions to rule out cases without objective bulimic episodes.

Abstract

Preserving patient dignity is a sentinel premise of palliative care. This study was conducted to gain a better understanding of factors influencing preservation of dignity in the last chapter of life.We conducted an open-ended written survey of 100 multidisciplinary providers (69% response rate) and responses were categorized to identify 2 main themes, 5 subthemes, and 10 individual factors that were used to create the preservation of dignity card-sort tool (p-DCT). The 10-item rank order tool was administered to a cohort of community dwelling Filipino Americans (n = 140, age mean = 61.3, 45% male and 55% female). A Spearman correlation matrix was constructed for all the 10 individual factors as well as the themes and subthemes based on the data generated by the subjects.The individual factors were minimally correlated with each other indicating that each factor was an independent stand-alone factor. The median, 25th and 75th percentile ranks were calculated and "s/he has self-respect" (intrinsic theme, self-esteem subtheme) emerged as the most important factor (mean rank 3.0 and median rank 2.0) followed by "others treat her/him with respect" (extrinsic theme, respect subtheme) with a mean rank = 3.6 and median = 3.0.The p-DCT is a simple, rank order card-sort tool that may help clinicians identify patients' perceptions of key factors influencing the preservation of their dignity in the last chapter of life.

Abstract

The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology (RUPP) Autism Network found an effect size of d = 1.2 in favor of risperidone on the main outcome measure in an 8-week double-blind, placebo-controlled trial for irritability in autistic disorder. This paper explores moderators and mediators of this effect.Intention-to-treat (ITT) analyses were conducted with suspected moderators and mediators entered into the regression equations. MacArthur Foundation Network subgroup guidelines were followed in the evaluation of the results.Only baseline severity moderated treatment response: Higher severity showed greater improvement for risperidone but not for placebo. Weight gain mediated treatment response negatively: those who gained more weight improved less with risperidone and more with placebo. Compliance correlated with outcome for risperidone but not placebo. Higher dose correlated with worse outcome for placebo, but not risperidone. Of nonspecific predictors, parent education, family income, and low baseline prolactin positively predicted outcome; anxiety, bipolar symptoms, oppositional-defiant symptoms, stereotypy, and hyperactivity negatively predicted outcome. Risperidone moderated the effect of change in 5'-nucleotidase, a marker of zinc status, for which decrease was associated with improvement only with risperidone, not with placebo.The benefit-risk ratio of risperidone is better with greater symptom severity. Risperidone can be individually titrated to optimal dosage for excellent response in the majority of children. Weight gain is not necessary for risperidone benefit and may even detract from it. Socioeconomic advantage, low prolactin, and absence of co-morbid problems nonspecifically predict better outcome. Mineral interactions with risperidone deserve further study.

Abstract

Despite high rates of psychiatric morbidity among young offenders, few studies look closely at prevalence rates in terms of race/ethnicity or developmental stage. Seven hundred and ninety (790) incarcerated young people with a mean age of 18+/-1.2 years were examined. The racial/ethnic distribution was White (17%), African American (28%), Hispanic (47%) and Other (8%). White males had greater than average levels of psychosis; African American males showed lower than average alcohol dependence rates but higher levels of marijuana dependence. White females were more likely than Hispanic and African American females to have attention deficit-hyperactivity disorder and substance and stimulant dependence. Race/ethnicity and age differences can be useful when creating culturally-informed and developmentally appropriate interventions for incarcerated young people.

Epidemiological Methods: About TimeINTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTHKraemer, H. C.2010; 7 (1): 29-45

Abstract

Epidemiological studies often produce false positive results due to use of statistical approaches that either ignore or distort time. The three time-related issues of focus in this discussion are: (1) cross-sectional vs. cohort studies, (2) statistical significance vs. public health significance, and (3), how risk factors "work together" to impact public health significance. The issue of time should be central to all thinking in epidemiology research, affecting sampling, measurement, design, analysis and, perhaps most important, the interpretation of results that might influence clinical and public-health decision-making and subsequent clinical research.

Abstract

To determine if improvement in mood would ameliorate autonomic dysregulation, HPA dysfunction, typical risk factors and C-reactive protein in depressed patients with elevated cardiovascular disease risk (CVD), 48 depressed participants with elevated cardiovascular risk factors were randomized to a cognitive behavioral intervention (CBT) or a waiting list control (WLC) condition. Twenty non-depressed age and risk-matched controls were also recruited. Traditional risk factors (e.g., lipids, blood pressure) and C-reactive protein were assessed pre- and post-treatment six months later. Subjects also underwent a psychophysiological stress test while cardiovascular physiology was measured. Salivary cortisol was measured during the day and during the psychological stress test. At post-treatment, the CBT subjects were significantly less depressed than WLC subjects. There was no significant difference in change scores on any of the traditional risk factors or C-reactive protein, cortisol measures, or cardiovascular physiology, except for triglyceride levels and heart rate, which were significantly lower in treatment compared to control subjects. The normal controls exhibited no change in the variables measured during the same time. A significant improvement in mood may have little impact on most traditional or atypical risk factors, cortisol or cardiophysiology.

Abstract

Patients often experience erosion of dignity as they cope with the dying process. Preserving patient dignity is a sentinel premise of palliative care. This study was conducted to gain a better understanding of factors influencing erosion of dignity at the end of life. We conducted an open-ended written survey of 100 multidisciplinary providers (69% response rate) and responses were categorized to identify 18 themes that were used to create a card-sort tool. The initial 18-item tool was administered to nurses (n = 83), nonhospice community-dwelling subjects (n = 190) and hospice patients (n = 26) and a principal component analysis (PCA) was used to identify the 6 primary factors. The key item in each factor as identified by the PCA was used to create the final 6-item dignity card-sort tool (DCT). The DCT was also administered to physicians caring for palliative care patients (n = 21). For each of the final 6 items, the correlation between the respondents (nurses, physicians, nonterminally ill subjects, and subjects receiving hospice care) was calculated using the Spearman's correlation coefficient. The nurses were very highly positively correlated with the physicians (correlation coefficient = 0.94) and the community-dwelling nonterminally ill subjects were highly positively correlated with the subjects receiving hospice care (correlation coefficient = 0.67). More importantly, both the nurses and physicians were negatively correlated with both community dwelling nonterminally ill subjects and the subjects receiving hospice care. The health professionals in the study felt that treating a patient with disrespect and not carrying out their wishes resulted in erosion of dignity. In contrast patients thought that poor medical care and untreated pain were the most important factors leading to erosion of dignity at life's end. The DCT is a promising tool that may help clinicians identify key factors resulting in perceptions of erosion of dignity in adult palliative care patients.

Abstract

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study was funded by the National Institute of Mental Health to compare the effectiveness of drugs for schizophrenia. The focus here is not on its conclusions but on the knotty issues of design and methods, in order to support appropriate clinical interpretation of the conclusions, and on using the CATIE experience to indicate directions for improvement of future clinical trials. While many of the CATIE design and implementation decisions are excellent and serve as models for future research, other decisions resulted in a study with a large study group but inadequate power. Multiple treatment interventions, unbalanced randomization within and across clinical sites, and multiple secondary outcomes are among the issues that require even more serious consideration in future large multisite clinical trials. Moreover, it is crucial to clarify whether the intent of a study is to establish superiority of some treatments or to establish equivalence, for the appropriate designs and analyses differ in these situations. If the study is designed, as was CATIE, to demonstrate some treatments' superiority, statistically nonsignificant results should not be misinterpreted as evidence of "equivalence." For establishing either superiority or equivalence, future treatment comparisons might better be designed with fewer sites, more subjects per site, fewer treatments, and fewer outcomes, in order to have the power for definitively establishing superiority or equivalence at a lower cost.

Abstract

The diagnosis of psychogenic nonepileptic seizures (PNES) can be challenging. In the absence of a gold standard to verify the reliability of the diagnosis by EEG-video, we sought to assess the interrater reliability of the diagnosis using EEG-video recordings.Patient samples consisted of 22 unselected consecutive patients who underwent EEG-video monitoring and had at least an episode recorded. Other test results and histories were not provided because the goal was to assess the reliability of the EEG-video. Data were sent to 22 reviewers, who were board-certified neurologists and practicing epileptologists at epilepsy centers. Choices were 1) PNES, 2) epilepsy, and 3) nonepileptic but not psychogenic ("physiologic") events. Interrater agreement was measured using a kappa coefficient for each diagnostic category. We used generalized kappa coefficients, which measure the overall level of between-method agreement beyond that which can be ascribed to chance. We also report category-specific kappa values.For the diagnosis of PNES, there was moderate agreement (kappa = 0.57, 95% confidence interval [CI] 0.39-0.76). For the diagnosis of epilepsy, there was substantial agreement (kappa = 0.69, 95% CI 0.51-0.86). For physiologic nonepileptic episodes, the agreement was low (kappa = 0.09, 95% CI 0.02-0.27). The overall kappa statistic across all 3 diagnostic categories was moderate at 0.56 (95% CI 0.41-0.73).Interrater reliability for the diagnosis of psychogenic nonepileptic seizures by EEG-video monitoring was only moderate. Although this may be related to limitations of the study (diagnosis based on EEG-video alone, artificial nature of the forced choice paradigm, single episode), it highlights the difficulties and subjective components inherent to this diagnosis.

Abstract

The objective of the study was to identify sex-specific psychopathologic predictors of criminal recidivism among a representative sample of incarcerated youths.In this prospective longitudinal study, the Mini-International Psychiatric Interview for children and adolescents was used to assess psychopathology in juveniles entering an Austrian pretrial detention facility between March 2003 and January 2005. From the beginning of the study until January 2006, data on criminal history were obtained from the Integrierte Vollzugsverwaltung, a database containing criminal information of every individual incarcerated in Austria. Of the 370 eligible participants, the final study sample comprised 328 juveniles (56 girls and 272 boys, age range = 14-21 years, mean = 16.7).Reincarceration rates within the specified follow-up period were 52.6% for the boys and 37.5% for the girls. Using Cox forward stepwise regression and Kaplan-Meier analyses, age at first incarceration (B = -.296, Wald statistic = 17.11, P < .001) and oppositional defiant disorder (B = .751, Wald statistic = 19.25, P < .001) were identified as significant predictors for reoffending in boys. In girls, generalized anxiety disorder (B = 1.97, Wald statistic = 13.71, P < .001) was found to be a predictor for reoffending, whereas dysthymia (B = -1.44, Wald statistic = 4.02, P = .045) was found to serve as protective factor.Our study confirms high rates of reoffending after release from correctional facilities in both sexes. It further defines sex-specific psychopathologic risk factors for relapse in incarcerated juveniles. According to our results, in boys, oppositional defiant disorder and early age at first incarceration are predictive of reincarceration. In girls, anxiety disorder was found to be a risk factor for future offending, whereas dysthymia was found to have a protective influence. Consequently, rehabilitation programs should be sex specific.

Abstract

To examine whether a group intervention including hypnosis can reduce cancer pain and trait hypnotizability would moderate these effects.This randomized clinical trial examined the effects of group therapy with hypnosis (supportive-expressive group therapy) plus education compared to an education-only control condition on pain over 12 months among 124 women with metastatic breast cancer.Pain and suffering, frequency of pain, and degree of constant pain were assessed at baseline and 4-month intervals. Those in the treatment group also reported on their experiences using the hypnosis exercises.Intention-to-treat analyses indicated that the intervention resulted in significantly less increase in the intensity of pain and suffering over time, compared to the education-only group, but had no significant effects on the frequency of pain episodes or amount of constant pain, and there was no interaction of the intervention with hypnotizability. Within the intervention group, highly hypnotizable participants, compared to those less hypnotizable, reported greater benefits from hypnosis, employed self-hypnosis more often outside of group, and used it to manage other symptoms in addition to pain.These results augment the growing literature supporting the use of hypnosis as an adjunctive treatment for medical patients experiencing pain.

Abstract

Beliefs about foods and binge eating may influence the development and maintenance of eating disorders and the likelihood that people will seek treatment. We found that the majority of a random sample of members of a large health maintenance organization considered binge eating a problem for which there are effective treatments. Self-reported binge eaters, however, were significantly less likely to agree that there are effective treatments. Two thirds of the sample reported that certain foods are addictive and also believed that strict dieting is an effective means of reducing binge eating. Therapeutic implications of these attitudes are discussed.

Abstract

Signal detection methods were used to identify values of metabolic variables that predict development of prediabetes or diabetes before (moderators) or associated with treatment (mediators), utilizing data from two multi-center clinical trials of patients with schizophrenia, treated for 6 months with olanzapine (OLZ) or ziprasidone (ZIP). At baseline, participants were often overweight/obese (63% with a body mass index >or=25.0kg/m(2)), dyslipidemic [more than one-third had elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations], and prediabetic (20%). Weight gain was significantly greater in OLZ-treated patients, as was accentuation of dyslipidemia. However, there were no significant correlations between weight gain and lipid changes from baseline to weeks 2, 4, 8 or to last observation. Type 2 diabetes developed in 4% and prediabetes in 18% of the population. Significant baseline predictors of diabetes were a HDL-C concentration <28mg/dL, or being >or=58-years-old if HDL-C concentration was >or=28mg/dL. Baseline plasma glucose concentration >or=92mg/dL was the only significant predictor of developing prediabetes, accounting for 60% of cases. Post-treatment increments in plasma TG concentrations >or=145mg/dL or >or=59mg/dL were significant predictors of diabetes (23%) or prediabetes (27%), respectively. If the increase in TG was <145mg/dL, rapid weight gain >or=6.1kg in 2 weeks predicted development of diabetes (18%). These findings provide a quantitative approach to identify those at greatest treatment-associated risk to develop glucose intolerance, and emphasize the need to address co-morbid medical disorders in these patients.

Abstract

Limitations of printed, text-based, consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity, such as those with schizophrenia. We conducted a randomized controlled comparison of the effectiveness of a multimedia vs routine consent procedure (augmented with a 10-minute control video presentation) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects. The primary outcome measure was manifest decisional capacity (understanding, appreciation, reasoning, and expression of choice) for participation in a (hypothetical) clinical drug trial, as measured with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the University of California San Diego (UCSD) Brief Assessment for Capacity to Consent (UBACC). The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition. Additional assessments included standardized measures of psychopathology and cognitive functioning. Relative to patients in the routine consent condition, schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR understanding and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition (as categorized with several previously established criteria). Among the healthy subjects, there were few significant effects of consent condition. These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity, particularly for complex and/or high-risk research protocols.

Abstract

To explore effects of various recruitment strategies on randomized clinical trial (RCT)-entry characteristics for patients with eating disorders within an everyday health-plan practice setting.Randomly selected women, aged 25-50, in a Pacific Northwest HMO were invited to complete a self-report binge-eating screener for two treatment trials. We publicized the trials within the health plan to allow self-referral. Here, we report differences on eating-disorder status by mode and nature of recruitment (online, mail, self-referred) and assessment (comprehensive versus abbreviated) and on possible differences in enrollee characteristics between those recruited by strategy (self-referred versus study-outreach efforts).Few differences emerged among those recruited through outreach who responded by different modalities (internet versus mail), early-versus-late responders, and those enrolling under more comprehensive or abbreviated assessment. Self-referred were more likely to meet binge-eating thresholds and reported higher average BMI than those recruited by outreach and responding by mail; however, in most respects the groups were more similar than anticipated. Fewer than 1% of those initially contacted through outreach enrolled.Aggressive outreach and screening is likely not feasible for broader dissemination in everyday practice settings and recruits individuals with more similar demographic and clinical characteristics to those recruited through more abbreviated and realistic screening procedures than anticipated.

Abstract

This study examined gender differences in prevalence of eating disorder symptoms including body image concerns (body checking or avoidance), binge eating, and inappropriate compensatory behaviors.A random sample of members (ages 18-35 years) of a health maintenance organization was recruited to complete a survey by mail or on-line. Items were drawn from the Patient Health Questionnaire and the Body Shape Questionnaire.Among the 3,714 women and 1,808 men who responded, men were more likely to report overeating, whereas women were more likely to endorse loss of control while eating. Although statistically significant gender differences were observed, with women significantly more likely than men to report body checking and avoidance, binge eating, fasting, and vomiting, effect sizes ("Number Needed to Treat") were small to moderate.Few studies of eating disorders include men, yet our findings suggest that a substantial minority of men also report eating disorder symptoms.

Abstract

This study examined prevalence rates of psychiatric disorders among young offenders after they were incarcerated for nine months.A total of 790 youths were surveyed, including a significant proportion of females (N=140, 18%), nine months after incarceration. The Structured Clinical Interview for DSM-IV with portions of the Diagnostic Interview for Children and Adolescents and the Structured Interview for DSM-IV Personality were used.Even when conduct disorder and oppositional defiant disorder were excluded, 88% of males and 92% of females had a psychiatric disorder (including substance use disorder); more than 80% of offenders met criteria for some type of substance use disorder. Gender differences were found for anxiety disorders (males 26%, females 55%, p

Abstract

The aim of this study was to compare a dimensional and a categorical approach to diagnosis, using as an illustration co-occurring symptoms of anxiety and depression concerning description, associations and predictive power. We analysed data from 60 869 individuals with valid ratings on the Hospital Anxiety and Depression Scale (HADS) and on mental impairment in the age range of 20 to 89 years of the cross-sectional Nord-Trøndelag Health Study 1995-1997. There was a wide variation of the dimensional symptom level (subscale scores) within both diagnostic categories (cut-offs > > or = 8 on both subscales), as is usually true with categorical and dimensional diagnosis. The dimensional (Spearman) correlation coefficients between anxiety and depression was 0.51 compared to 0.38 for the categorical. The power to predict impairment was weaker with the categorical than with the dimensional approach of the HADS, showing fewer statistically significant coefficients in the logistic regression models and lower area under curve (0.82 versus 0.87). This is an example illustrating the impact use of dimensional diagnoses would have on research and clinical practice.

Abstract

Many childhood psychiatric problems are transient. Consequently, screening procedures to accurately identify children with problems unlikely to remit and thus, in need of intervention, are of major public health concern. This study aimed to develop a universal school-based screening procedure based on the answers to three questions: (1) What are the broad patterns of mental health problems from kindergarten to grade 5? (2) What are the grade 5 outcomes of these patterns? (3) How early in school can children likely to develop the most impairing patterns be identified accurately?Mothers and teachers reported on a community sample (N = 328) of children's internalizing and externalizing symptoms in kindergarten and grades 1, 3, and 5. In grade 5, teachers reported on children's school-based functional impairments, physical health problems, and service use; mothers reported on children's specialty mental health care.Four patterns distinguished children who (1) never evidenced symptoms; (2) evidenced only isolated symptoms; or evidenced recurrent symptoms, either (3) without or (4) with comorbid internalizing and externalizing. By grade 5, children with recurrent comorbid symptoms had the greatest impairments, physical health problems, and service use. These children can be identified quite accurately by grade 1.Universal screening at school entry can effectively identify children likely to develop recurrent comorbid symptoms, and would provide a basis for developing optimal targeted intervention programs.

Abstract

The purpose of this study was to develop and validate a self-report measure of body image and sexual adjustment in breast cancer patients: the Sexual Adjustment and Body Image Scale (SABIS). Three hundred and fifty three women diagnosed with primary breast cancer that had completed initial surgical treatment completed the SABIS and five measures of psychological, psychosocial, and sexual functioning. Psychometric properties of the SABIS were examined and it was found to be a reliable and valid means of assessing body image and sexuality in breast cancer patients following surgery.

Abstract

The terrorist attacks of September 11, 2001 inflicted distress beyond those directly exposed, thereby providing an opportunity to examine the contributions of a range of factors (cognitive, emotional, social support, coping) to psychological resilience for those indirectly exposed. In an Internet convenience sample of 1281, indices of resilience (higher well-being, lower distress) at baseline (2.5-12 weeks post-attack) were each associated with less emotional suppression, denial and self-blame, and fewer negative worldview changes. After controlling for initial outcomes, baseline negative worldview changes and aspects of social support and coping all remained significant predictors of 6-month outcomes, with worldview changes bearing the strongest relationship to each. These findings highlight the role of emotional, coping, social support, and particularly, cognitive variables in adjustment after terrorism.

Abstract

Results in risk studies based on events per person-time (EPT, technically 'incidence rate') often prove non-confirmable. The circumstances in which the EPT-ratio is unquestionably both valid and optimal to compare a high- and low-risk group, a constant hazards situation, are discussed. However, the constant hazards situation seldom applies in medical research. When the constant hazards situation does not apply, even under optimal circumstances, with fixed entry time and follow-up time for all those not experiencing the event and absence of censoring, EPT-ratio yields at best ambiguous, at worst misleading, results. More careful design and survival analyses are recommended in place of use of EPTs.

Abstract

Since the time of Kraeplin, schizophrenia has been thought of as a disorder with progressive deterioration in functioning. An important aspect of functioning is both physical and mental health-related quality of life (HRQoL). The objective of this study was to examine the relationship of age to both mental and physical aspects of HRQoL in individuals with schizophrenia as compared to normal comparison subjects (NCs).Middle-aged and older community-dwelling patients with schizophrenia (N=486) were compared to NCs (N=101). Health related quality of life was measured using the SF-36 Physical Health and Mental Health Component scores. The relationship between age and HRQoL was examined using linear regressions. In addition, we performed exploratory analyses to examine the effects of confounding variables on this relationship, and to examine the effects of age on SF-36 subscales.Patients with schizophrenia had lower SF-36 Physical and Mental Health Component scores than NCs, and these differences persisted after adjusting for the age difference between the two groups. The relationship between age and mental, but not physical, HRQoL was significantly different between the patients with schizophrenia and the NCs. Specifically, older age was associated with higher mental HRQoL among patients with schizophrenia, but not among the NCs. This difference remained significant after examining multiple potential confounding demographic and clinical variables.This study found that older age was associated with greater mental health quality of life. Longitudinal studies are warranted to confirm our finding, and to examine potential mechanisms responsible for possible improvement in mental HRQoL with age.

Abstract

The basic principles underlying randomized clinical trials have been known for more than 50 years. The Consolidated Standards of Reporting Trials (CONSORT) guidelines, published in 1996 and based on those principles, are a valuable guide to what needs to be reported from any trial within word-limit constraints, but they do not provide guidelines to the decisions that have to be made to generate a trial with credible results. Using these guidelines as do J. C. Coyne, M. Stefanek, and S. C. Palmer (2007) is a misinterpretation of their purpose. Furthermore, Coyne et al. misrepresented the methods and findings of studies of the effects of psychosocial intervention on cancer survival. These errors are systematically reviewed. The results of these questionable analyses led Coyne et al. to recommend stopping research in an area that may be highly productive. Recent developments in the field are summarized. It is a mistaken and dangerous conclusion to declare this or other areas of scientific research off limits.

Abstract

The development of new antidepressant drugs has reached a plateau. There is an unmet need for faster, better, and safer medications, but as placebo-response rates rise, effect sizes shrink, and more studies fail or are negative, pharmaceutical companies are increasingly reluctant to invest in new drug development because of the risk of failure. In the absence of an identifiable human pathophysiology that can be modeled in preclinical studies, the principal point of leverage to move beyond the present dilemma may be improving the information gleaned from well-designed proof-of-concept (POC) studies of new antidepressant drugs with novel central nervous system effects. With this in mind, a group of experts was convened under the auspices of the University of Arizona Department of Psychiatry and Best Practice Project Management, Inc.Forty-five experts in the study of antidepressant drugs from academia, government (U.S. Food and Drug Administration and National Institute of Mental Health), and industry participated. EVIDENCE/CONSENSUS PROCESS: In order to define the state of clinical trials methodology in the antidepressant area, and to chart a way forward, a 2-day consensus conference was held June 21-22, 2007, in Bethesda, Md., at which careful reviews of the literature were presented for discussion. Following the presentations, participants were divided into 3 workgroups and asked to address a series of separate questions related to methodology in POC studies. The goals were to review the history of antidepressant drug trials, discuss ways to improve study design and data analysis, and plan more informative POC studies.The participants concluded that the federal government, academic centers, and the pharmaceutical industry need to collaborate on establishing a network of sites at which small, POC studies can be conducted and resulting data can be shared. New technologies to analyze and measure the major affective, cognitive, and behavioral components of depression in relationship to potential biomarkers of response should be incorporated. Standard assessment instruments should be employed across studies to allow for future meta-analyses, but new instruments should be developed to differentiate subtypes and symptom clusters within the disorder that might respond differently to treatment. Better early-stage POC studies are needed and should be able to amplify the signal strength of drug efficacy and enhance the quality of information in clinical trials of new medications with novel pharmacologic profiles.

Abstract

This study examined healthcare services used by adults diagnosed with an eating disorder (ED) in a large health maintenance organization in the Pacific Northwest.Electronic medical records were used to collect information on all out-patient and in-patient visits and medication dispenses, from 2002 to 2004, for adults aged 18-55 years who received an ED diagnosis during 2003. Healthcare services received the year prior to, and following, the receipt of an ED diagnosis were examined. Cases were matched to five comparison health plan members who had a health plan visit close to the date of the matched case's ED diagnosis.Incidence of EDs (0.32% of the 104,130 females, and 0.02% of the 93,628 males) was consistent with prior research employing treatment-based databases, though less than community-based samples. Most cases (50%) were first identified during a primary-care visit and psychiatric co-morbidity was high. Health services use was significantly elevated in all service sectors among those with an ED when compared with matched controls both in the year preceding and that following the receipt of the incident ED diagnosis. Contrary to expectations, healthcare utilization was found to be similarly high across the spectrum of EDs (anorexia nervosa, bulimia nervosa, and eating disorders not otherwise specified).The elevation in health service use among women both before and after diagnosis suggests that EDs merit identification and treatment efforts commensurate with other mental health disorders (e.g. depression) which have similar healthcare impact.

Abstract

To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the assimilation of cognitive training by older adults with memory complaints, we gave 168 nondemented, community-dwelling volunteers with memory complaints either 5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double-blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6 weeks before a 2-week course of cognitive training and was maintained for the remainder of a year. Cognitive training improved performance; donepezil was well tolerated. However, there were no significant benefits of donepezil compared with placebo. An additional dose-ranging study with a starting dose of 5 mg a day suggests that the high dose was not the reason. Physiological tolerance may occur with chronic donepezil treatment and may increase AChE levels; this may be why short-term studies have shown the benefit of AChE inhibitor use in nondemented participants whereas chronic use has failed to enhance cognition.

Abstract

There is an ongoing debate about the definitions and clinical significance of night eating syndrome (NES). This study explored potential subtypes based on night eating patterns and features reported to be associated, with NES in a representative community sample of 8,250 individuals aged 15-39 years.Latent class analysis was used to identify NES subtypes among 2,068 participants who reported night eating behavior.A four-class solution was judged best. Two classes appear to characterize individuals who eat very late or eat a large proportion of their daily intake after 7 pm, and two other classes are characterized by high rates of depressive symptoms. Results do not support an association between night eating and obesity in young adults. Late night eating is associated with high caloric intake, high sodium intake, and low protein intake.Evidence supports the validity of a definition of NES based on eating very late at night.

Abstract

To review the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published over the past decade as three sets of articles.In a two-part article-Part I: Executive Summary (without distracting details) and Part II: Supporting Details (with additional background and detail required by the complexity of the MTA)-we address confusion and controversy about the findings.We discuss the basic features of the gold standard used to produce scientific evidence, the randomized clinical trial, for which was used to contrast four treatment conditions: medication management alone (MedMgt), behavior therapy alone (Beh), the combination of these two (Comb), and a community comparison of treatment "as usual" (CC). For each of the three assessment points we review three areas that we believe are important for appreciation of the findings: definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term, and qualification of the interim conclusions about long-term effects of treatments for ADHD.We discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD.

Abstract

To review and provide details about the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published during the past decade as three sets of articles.In the second of a two part article, we provide additional background and detail required by the complexity of the MTA to address confusion and controversy about the findings outlined in part I (the Executive Summary).We present details about the gold standard used to produce scientific evidence, the randomized clinical trial (RCT), which we applied to evaluate the long-term effects of two well-established unimodal treatments, Medication Management (MedMGT) and behavior therapy (Beh), the multimodal combination (Comb), and treatment "as usual" in the community (CC). For each of the first three assessment points defined by RCT methods and included in intent-to-treat analyses, we discuss our definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term varying from weeks to years, and qualification of the interim conclusions about long-term effects of treatments for ADHD based on many exploratory analyses described in additional published articles.Using a question and answer format, we discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD.

Abstract

The main aim of the present novel reanalysis of archival data was to compare the time to remission during 12 weeks of treatment of chronic depression following antidepressant medication (n = 218), psychotherapy (n = 216), and their combination (n = 222). Cox regression survival analyses revealed that the combination of medication and psychotherapy produced full remission from chronic depression more rapidly than either of the single modality treatments, which did not differ from each other. Receiver operating characteristic curve analysis was used to explore predictors (treatment group, demographic, clinical, and psychosocial) of remission. For those receiving the combination treatment, the most likely to succeed were those with low baseline depression (24-item Hamilton Rating Scale for Depression [HRSD; M. Hamilton, 1967] score < 26) and those with high depression scores but low anxiety (HRSD = 26 and Hamilton Anxiety Rating Scale [M. Hamilton, 1959] < 14). Both profiles were associated with at least 40% chance of attaining full remission. The model did not identify predictors for those receiving medication or psychotherapy alone, and it did not distinguish between the 2 monotherapies. The authors conclude that combined antidepressant medications and psychotherapy result in faster full remission of chronic forms of major depressive disorder.

Abstract

Atypical antipsychotic drugs have been used off label in clinical practice for treatment of serious dementia-associated agitation and aggression. Following reports of cerebrovascular adverse events associated with the use of atypical antipsychotics in elderly patients with dementia, the U.S. Food and Drug Administration (FDA) issued black box warnings for several atypical antipsychotics titled "Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients With Dementia." Subsequently, the FDA initiated a metaanalysis of safety data from 17 registration trials across 6 antipsychotic drugs (5 atypical antipsychotics and haloperidol). In 2005, the FDA issued a black box warning regarding increased risk of mortality associated with the use of atypical antipsychotic drugs in this patient population.Geriatric mental health experts participating in a 2006 consensus conference (Bethesda, Md., June 28-29) reviewed evidence on the safety and efficacy of antipsychotics, as well as nonpharmacologic approaches, in treating dementia-related symptoms of agitation and aggression. EVIDENCE/CONSENSUS PROCESS: The participants concluded that, while problems in clinical trial designs may have been one of the contributors to the failure to find a signal of drug efficacy, the findings related to drug safety should be taken seriously by clinicians in assessing the potential risks and benefits of treatment in a frail population, and in advising families about treatment. Information provided to patients and family members should be documented in the patient's chart. Drugs should be used only when nonpharmacologic approaches have failed to adequately control behavioral disruption. Participants also agreed that there is a need for an FDA-approved medication for the treatment of severe, persistent, or recurrent dementia-related symptoms of agitation and aggression (even in the absence of psychosis) that are unresponsive to nonpharmacologic intervention.This article outlines methodological enhancements to better evaluate treatment approaches in future registration trials and provides an algorithm for improving the treatment of these patients in nursing home and non-nursing home settings.

Abstract

Similar to other fields, a targeted behavioral medicine perspective can aid decision-making related to participant-intervention matching.To present one potentially useful definition of intervention targeting activity; describe potential targeting domains of particular relevance to behavioral medicine; discuss different statistical approaches to aid the targeted intervention development process; and discuss the challenges and opportunities accompanying the incorporation of targeted intervention development methods into behavioral randomized clinical trial (RCT) research.Drawing from recent conceptual work by the MacArthur group and other scientists in the field, methods and approaches to undertaking moderator analysis are discussed.Examples of moderator analyses are provided which reflect the different statistical methods and variable domains that may serve as moderators of intervention success.The recommended exploratory work can help to make the most efficient use of RCTs to identify the best paths for subsequent RCT development in a resource-constrained era.

Abstract

There is growing realization of the importance in randomized clinical trails (RCTs) and in risk research of understanding, not merely that a treatment or a risk factor has an effect on the outcome but specifically on whom in the population sampled does a treatment or a risk factor have such effects (via moderators), how those effects might be achieved (via mediators), and how clinically significant such effects might be (via effect sizes). Classic methods of detection of moderators and mediators have been based on statistical significance in linear models, procedures that often produce inconsistent results hard to interpret in terms of clinical significance. Methods based on non-parametric methods specifically designed to facilitate considerations of clinical significance are here introduced for binary moderators and mediators and the discussion opened for what would be needed in general.

Abstract

The aim is to evaluate the effectiveness of a manualized 12-week supportive-expressive group therapy program among primary breast cancer patients treated in community settings, to determine whether highly distressed patients were most likely to benefit and whether therapist's training or experience was related to outcome.Three hundred and fifty-three women within one year of diagnosis with primary breast cancer were randomly assigned to receive supportive-expressive group therapy or to an education control condition. Participants were recruited from two academic centers and nine oncology practices, which were members of NCI's Community Clinical Oncology Program (CCOP) and were followed over 2 years.A 2x2x19 analysis of variance was conducted with main effects of treatment condition, cohort, and baseline distress and their interactions. There was no main effect for treatment condition after removing one subject with an extreme score. Highly distressed women did not derive a greater benefit from treatment. Therapist training and psychotherapy experience were not associated with a treatment effect.This study provides no evidence of reduction in distress as the result of a brief supportive-expressive intervention for women with primary breast cancer. Future studies might productively focus on women with higher initial levels of distress.

Abstract

In recognition of the increasingly important role of moderators and mediators in clinical research, clear definitions are sought of the two terms to avoid inconsistent, ambiguous, and possibly misleading results across clinical research studies.The criteria used to define moderators and mediators proposed by the Baron & Kenny approach, which have been long used in social/behavioral research, are directly compared to the criteria proposed by the recent MacArthur approach, which modified the Baron & Kenny criteria.After clarifying the differences in criteria between approaches, the rationale for the modifications is clarified and the implications for the design and interpretation of future studies considered.Researchers may find modifications introduced in the MacArthur approach more appropriate to their research objectives, particularly if their research might have a direct influence on decision making.

Abstract

Detection of preclinical cognitive deficits is important for identifying those at greatest risk for such disorders as Alzheimer's disease. However, available neuropsychological measures may not be sufficiently sensitive to preclinical cognitive impairment, particularly in high functioning or younger older adults. This study utilizes a battery of computerized cognitive tests (Cognometer) designed to provide a more sensitive measure of age-related cognitive performance by incorporating speed-of-processing components. Fifty-one community-dwelling older adults were administered the Cognometer battery, which incorporates speed-of-processing components into measures of verbal, spatial and working memory, attention, and visuo-spatial ability. Performance of 18 subjects with the epsilon4 allele was compared to that of 33 subjects without the epsilon4 allele. A brief battery of standard neuropsychological measures was also administered. No significant differences were observed between the two groups with respect to performance on any of the neuropsychological measures. However, with respect to the Cognometer battery, individuals with the epsilon4 allele were significantly slower in performing all the cognitive tasks, with the exception of the visuo-spatial task. With respect to performance, the two genotype groups did not differ significantly except on immediate memory, with the epsilon4 group exhibiting increased errors. Overall, the epsilon4 group was significantly slower in performing all of the Cognometer memory tasks. These findings provide continued support for the negative impact of the epsilon4 allele on cognition and further suggest that speed-of-processing during memory tasks may have the potential to detect subtle cognitive deficits.

Abstract

The lack of an accepted standard for measuring cognitive change in schizophrenia has been a major obstacle to regulatory approval of cognition-enhancing treatments. A primary mandate of the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was to develop a consensus cognitive battery for clinical trials of cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures.The MATRICS Neurocognition Committee evaluated more than 90 tests in seven cognitive domains to identify the 36 most promising measures. A separate expert panel evaluated the degree to which each test met specific selection criteria. Twenty tests were selected as a beta battery. The beta battery was administered to 176 individuals with schizophrenia and readministered to 167 of them 4 weeks later so that the 20 tests could be compared directly.The expert panel ratings are presented for the initially selected 36 tests. For the beta battery tests, data on test-retest reliability, practice effects, relationships to functional status, practicality, and tolerability are presented. Based on these data, 10 tests were selected to represent seven cognitive domains in the MATRICS Consensus Cognitive Battery.The structured consensus method was a feasible and fair mechanism for choosing candidate tests, and direct comparison of beta battery tests in a common sample allowed selection of a final consensus battery. The MATRICS Consensus Cognitive Battery is expected to be the standard tool for assessing cognitive change in clinical trials of cognition-enhancing drugs for schizophrenia. It may also aid evaluation of cognitive remediation strategies.

Abstract

To determine how neuroanatomic variation in children and adolescents with fragile X syndrome is linked to reduced levels of the fragile X mental retardation-1 protein and to aberrant cognition and behavior.This study included 84 children and adolescents with the fragile X full mutation and 72 typically developing control subjects matched for age and sex. Brain morphology was assessed with volumetric, voxel-based, and surface-based modeling approaches. Intelligence quotient was evaluated with standard cognitive testing, whereas abnormal behaviors were measured with the Autism Behavior Checklist and the Aberrant Behavior Checklist.Significantly increased size of the caudate nucleus and decreased size of the posterior cerebellar vermis, amygdala, and superior temporal gyrus were present in the fragile X group. Subjects with fragile X also demonstrated an abnormal profile of cortical lobe volumes. A receiver operating characteristic analysis identified the combination of a large caudate with small posterior cerebellar vermis, amygdala, and superior temporal gyrus as distinguishing children with fragile X from control subjects with a high level of sensitivity and specificity. Large caudate and small posterior cerebellar vermis were associated with lower fragile X mental retardation protein levels and more pronounced cognitive deficits and aberrant behaviors.Abnormal development of specific brain regions characterizes a neuroanatomic phenotype associated with fragile X syndrome and may mediate the effects of FMR1 gene mutations on the cognitive and behavioral features of the disorder. Fragile X syndrome provides a model for elucidating critical linkages among gene, brain, and cognition in children with serious neurodevelopmental disorders.

Abstract

African-American girls and women are at high risk of obesity and its associated morbidities. Few studies have tested obesity prevention strategies specifically designed for African-American girls. This report describes the design and baseline findings of the Stanford GEMS (Girls health Enrichment Multi-site Studies) trial to test the effect of a two-year community- and family-based intervention to reduce weight gain in low-income, pre-adolescent African-American girls.Randomized controlled trial with measurements scheduled in girls' homes at baseline, 6, 12, 18 and 24 month post-randomization.Low-income areas of Oakland, CA.Eight, nine and ten year old African-American girls and their parents/caregivers.Girls are randomized to a culturally-tailored after-school dance program and a home/family-based intervention to reduce screen media use versus an information-based community health education Active-Placebo Comparison intervention. Interventions last for 2 years for each participant.Change in body mass index over the two-year study.Recruitment and enrollment successfully produced a predominately low-socioeconomic status sample. Two-hundred sixty one (261) families were randomized. One girl per family is randomly chosen for the analysis sample. Randomization produced comparable experimental groups with only a few statistically significant differences. The sample had a mean body mass index (BMI) at the 74 th percentile on the 2000 CDC BMI reference, and one-third of the analysis sample had a BMI at the 95th percentile or above. Average fasting total cholesterol and LDL cholesterol were above NCEP thresholds for borderline high classifications. Girls averaged low levels of moderate to vigorous physical activity, more than 3 h per day of screen media use, and diets high in energy from fat.The Stanford GEMS trial is testing the benefits of culturally-tailored after-school dance and screen-time reduction interventions for obesity prevention in low-income, pre-adolescent African-American girls.

Abstract

To evaluate a developmental psychopathology approach for understanding adolescent social anxiety, parent-reported predictors of social anxiety were examined in a nonclinical sample of adolescents. Structured diagnostic interviews were obtained from biological parents of 770 participants. Potential risk factors assessed included child characteristics: negative affect, shyness, separation anxiety disorder, and childhood chronic illness, as well as parent characteristics: major depression, panic disorder, and agoraphobia. Adolescent social anxiety was measured multiple times during high school. Findings indicate stability in social anxiety symptoms across time. Parent-reported, childhood negative affect, shyness, and chronic illness as well as parental panic disorder or agoraphobia were associated with adolescent social anxiety. Interactions were observed between parent-reported childhood shyness and gender and between parent-reported childhood shyness and parent-reported childhood chronic illness in the prediction of social anxiety. Parent-reported childhood shyness was a stronger predictor of adolescent social anxiety in females compared to males. The combined effect of subjects being positive for both parent-reported childhood shyness and parent-reported childhood chronic illness was greater than would be expected based on additive effects. This study provides support for a multifactorial and developmentally informed understanding of adolescent social anxiety.

Abstract

To date, no cross-national RCT has addressed the mechanisms underlying the relative success of pharmacological and psychotherapeutic interventions for depression. A multi-site clinical trial that includes psychotherapy as one of the treatments presents numerous challenges related to cross-site consistency and communication.This report describes how those challenges were met in the study "Depression: The Search for Treatment Relevant Phenotypes'', being carried out at the University of Pittsburgh and the University of Pisa, Italy.Implementing the study required the investigators to address methodological and practical challenges related to the different requirements of the two Institutional Review Boards (IRBs), psychotherapy training, independent evaluator training, patient recruitment, development of common tools for data entry, quality control and generation of weekly reports of patient progress as well as establishing a similar clinical and research framework in two countries with substantially different health care systems.By having bilingual investigators and staff members who spent time at one another's sites, making use of frequent conference-call staff meetings and being flexible within the bounds of the sometimes contradictory requirements of the IRBs, the investigators were able to meet the human subjects protection requirements of both institutions, surmount language barriers to consistent therapist and evaluator training and develop common tools for study management. As a result, recruitment goals were met at both sites and retention rates were high. One instance of inconsistent implementation of the protocol was corrected within the first year.This study was conducted in two Western cultures by researchers with long-standing collaboration. Our findings may not be generalizable to other countries or research settings.The implementation of a cross-national protocol and the adoption and maintenance of common procedures is possible when investigators are aware of the challenges this may present and are proactive in trying to address them.

Abstract

To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients.AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria.The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was approximately 0.25 points for the 91 patients receiving donepezil and approximately 2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained.A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.

Abstract

The purpose of our study was to investigate the long-term effect of mnemonic training on memory performance in older adults. Five years after participation in a mnemonic training study, we followed-up 112 community-dwelling older adults, 60 years of age and over. Delayed recall of a word list was assessed prior to, and immediately following mnemonic training, and at the 5-year follow-up. Overall, there was no significant difference between word recall prior to training and that exhibited at follow-up. However, pre-training performance, gain scores in performance immediately post-training and use of the mnemonic predicted performance at follow-up. Individuals who self-reported using the mnemonic exhibited the highest performance overall, with scores significantly higher than at pre-training. Our findings suggest that mnemonic training has long-term benefits for some older adults, particularly those who continue to employ the mnemonic.

Abstract

Delinquent juveniles are at extreme risk for suicide with death rates 4 times higher than in the general population. Whereas psychopathologic risk factors for suicidal behavior in nonforensic adolescent populations are well defined, psychopathologies associated with suicidality in delinquent juveniles are not yet clear. The objective of this study was to determine gender-specific psychopathologic profiles associated with suicidality in detained juveniles.The Massachusetts Youth Screening Instrument-Second Version, the Youth Self-Report, and the Mini-International Neuropsychiatric Interview for children and adolescents were used to investigate juveniles in an Austrian pre-trial detention facility. The study sample consisted of all juveniles entering the system between March 2003 and January 2005. Of the 370 eligible participants, 319 completed the study (53 girls and 266 boys; age range, 14 to 21 years; mean = 16.67, SD = 1.45 years).We found significantly higher prevalence rates of both current (p < .01) and lifetime (p < .001) suicidality in girls than in boys. Suicidal boys exhibited more psychopathology and a wider range of psychopathology compared to nonsuicidal boys. For suicidal girls, psychopathologies appeared more circumscribed (all relevant p values < .04). Using signal detection methods, major depressive disorder, attention-deficit/hyperactivity disorder, and social phobia identified boys at highest risk of suicidality, while a diagnosis of posttraumatic stress disorder identified girls at highest risk.Suicidality levels are high in delinquent adolescents, especially in girls. Psychopathologic risk factors seem to be gender specific in this population. Not only depression, but also psychopathologies that usually do not arouse strong suspicion for an association with suicidal behavior, i.e., social phobia and ADHD in boys and PTSD in girls, might increase suicide risk. Further research in other countries is needed to replicate our results with respect to sociocultural influences.

Abstract

This study was designed to replicate our earlier finding that intensive group therapy extended survival time of women with metastatic breast cancer. Subsequent findings concerning the question of whether such psychosocial support affects survival have been mixed.One hundred twenty-five women with confirmed metastatic (n = 122) or locally recurrent (n = 3) breast cancer were randomly assigned either to the supportive-expressive group therapy condition (n = 64), where they received educational materials plus weekly supportive-expressive group therapy, or to the control condition (n = 61), where they received only educational materials for a minimum of 1 year. The treatment, 90 minutes once a week, was designed to build new bonds of social support, encourage expression of emotion, deal with fears of dying and death, help restructure life priorities, improve communication with family members and healthcare professionals, and enhance control of pain and anxiety.Overall mortality after 14 years was 86%; median survival time was 32.8 months. No overall statistically significant effect of treatment on survival was found for treatment (median, 30.7 months) compared with control (median, 33.3 months) patients, but there was a statistically significant intervention site-by-condition interaction. Exploratory moderator analysis to explain that interaction revealed a significant overall interaction between estrogen-receptor (ER) status and treatment condition (P = .002) such that among the 25 ER-negative participants, those randomized to treatment survived longer (median, 29.8 months) than ER-negative controls (median, 9.3 months), whereas the ER-positive participants showed no treatment effect.The earlier finding that longer survival was associated with supportive-expressive group therapy was not replicated. Although it is possible that psychosocial effects on survival are relevant to a small subsample of women who are more refractory to current hormonal treatments, further research is required to investigate subgroup differences.

Abstract

This study examined a broad range of childhood risk factors for binge-eating disorders (bulimia nervosa or binge eating disorder, BN/BED), utilizing data that had been collected prospectively in the 10-year National Heart, Lung, and Blood Institute Growth and Health Study.Forty-five women with a history of BED/BN (with onset age > 14 and <20 years) and 1,515 women who did not have a history of an eating disorder were included.Signal detection analysis indicated a single pathway that identified approximately 13% of the BED/BN cases. The pathway was based on an elevated level of perceived stress prior to the age of 14.Our findings suggest that eating disorders may have multiple and complex etiologies. This is the first study to suggest that elevated levels of perceived stress may precede the onset of binge-eating disorders. Whether this is a causal association remains a question.

Abstract

To examine the effects of cumulative, real-world marketing and brand exposures on young children by testing the influence of branding from a heavily marketed source on taste preferences.Experimental study. Children tasted 5 pairs of identical foods and beverages in packaging from McDonald's and matched but unbranded packaging and were asked to indicate if they tasted the same or if one tasted better.Preschools for low-income children.Sixty-three children (mean +/- SD age, 4.6 +/- 0.5 years; range, 3.5-5.4 years).Branding of fast foods.A summary total taste preference score (ranging from -1 for the unbranded samples to 0 for no preference and +1 for McDonald's branded samples) was used to test the null hypothesis that children would express no preference.The mean +/- SD total taste preference score across all food comparisons was 0.37 +/- 0.45 (median, 0.20; interquartile range, 0.00-0.80) and significantly greater than zero (P

Abstract

There is a critical need for practical measures for screening and documenting decisional capacity in people participating in different types of clinical research. However, there are few reliable and validated brief tools that could be used routinely to evaluate individuals' capacity to consent to a research protocol.To describe the development, testing, and proposed use of a new practical instrument to assess decision-making capacity: the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC). The UBACC is intended to help investigators identify research participants who warrant more thorough decisional capacity assessment and/or remediation efforts prior to enrollment.We developed the UBACC as a 10-item scale that included questions focusing on understanding and appreciation of the information concerning a research protocol. It was developed and tested among middle-aged and older outpatients with schizophrenia and healthy comparison subjects participating in research on informed consent. In an investigation of reliability and validity, we studied 127 outpatients with schizophrenia or schizoaffective disorder and 30 healthy comparison subjects who received information about a simulated clinical drug trial. Internal consistency, interrater reliability, and concurrent (criterion) validity (including correlations with an established instrument as well as sensitivity and specificity relative to 2 potential "gold standard" criteria) were measured.Reliability and validity of the UBACC.The UBACC was found to have good internal consistency, interrater reliability, concurrent validity, high sensitivity, and acceptable specificity. It typically took less than 5 minutes to administer, was easy to use and reliably score, and could be used to identify subjects with questionable capacity to consent to the specific research project.The UBACC is a potentially useful instrument for screening large numbers of subjects to identify those needing more comprehensive decisional capacity assessment and/or remediation efforts.

Abstract

The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.

DSM categories and dimensions in clinical and research contextsINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCHKraemer, H. C.2007; 16: S8-S15

Abstract

An enhancement to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) is currently under consideration, one that would enhance both the reliability and validity of the Diagnostic and Statistical Manual (DSM) diagnoses: the addition of a dimensional adjunct to each of the traditional categorical diagnoses of the DSM. We first review the history and context of this proposal and define the concepts on which this dimensional proposal is based. The advantages of dimensional measures over categorical measures have long been known, but we here illustrate what is known with a theoretical and a practical demonstration of the potential effects of this addition. Possible objections to the proposal are discussed, concluding with some general criteria for implementing this proposal.

Abstract

To investigate temperament-creativity relationships in euthymic bipolar (BP) and unipolar major depressive (MDD) patients, creative discipline controls (CC), and healthy controls (HC).49 BP, 25 MDD, 32 CC, and 47 HC (all euthymic) completed three self-report temperament/personality measures: the Revised NEO Personality Inventory (NEO-PI-R), the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), and the Temperament and Character Inventory (TCI); and four creativity measures yielding six parameters: the Barron-Welsh Art Scale (BWAS-Total, BWAS-Like, and BWAS-Dislike), the Adjective Check List Creative Personality Scale (ACL-CPS), and the Torrance Tests of Creative Thinking--Figural (TTCT-F) and Verbal (TTCT-V) versions. Factor analysis was used to consolidate the 16 subscales from the three temperament/personality measures, and the resulting factors were assessed in relationship to the creativity parameters.Five personality/temperament factors emerged. Two of these factors had prominent relationships with creativity measures. A Neuroticism/Cyclothymia/Dysthymia Factor, comprised mostly of NEO-PI-R-Neuroticism and TEMPS-A-Cyclothymia and TEMPS-A-Dysthymia, was related to BWAS-Total scores (r=0.36, p<0.0001) and BWAS-Dislike subscale scores (r=0.39, p<0.0001). An Openness Factor, comprised mostly of NEO-PI-R-Openness, was related to BWAS-Like subscale scores (r=0.28, p=0.0006), and to ACL-CPS scores (r=0.46, p<0.0001). No significant relationship was found between temperament/personality and TTCT-F and TTCT-V scores.Neuroticism/Cyclothymia/Dysthymia and Openness appear to have differential relationships with creativity. The former could provide affective (Neuroticism, i.e. access to negative affect, and Cyclothymia, i.e. changeability of affect) and the latter cognitive (flexibility) advantages to enhance creativity. Further studies are indicated to clarify mechanisms of creativity and its relationships to affective processes and bipolar disorders.

Abstract

We examined the relation between measures of body size and mortality in a predominantly White cohort of 8029 women aged 65 years and older who were participating in the Study of Osteoporotic Fractures.Body composition measures (fat and lean mass and percentage body fat) were calculated by bioelectrical impedance analysis. Anthropometric measures were body mass index (BMI; kg/m2) and waist circumference.During 8 years of follow-up, there were 945 deaths. Mortality was lowest among women in the middle of the distribution of each body size measure. For BMI, the lowest mortality rates were in the range 24.6 to 29.8 kg/m2. The U-shaped relations were seen throughout the age ranges included in this study and were not attributable to smoking or measures of preexisting illness. Body composition measures were not better predictors of mortality than BMI or waist girth.Our results do not support applying the National Institutes of Health categorization of BMI from 25 to 29.9 kg/m2 as overweight in older women, because women with BMIs in this range had the lowest mortality.

Abstract

In February of 2004, the American Psychiatric Institute for Research and Education (APIRE) hosted a Launch and Methodology Conference to discuss the role statistics might play in the eventual revision of the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Ninth Edition of the International Classification of Diseases (ICD9). The conference consisted of talks on specific topics by statisticians and epidemiologists from North America and Great Britain, followed by group discussion by experts in nosology and psychopathology. We report here on the development of specific themes related to the future interaction between statisticians and nosologists in DSM-V development that arose as a result of that meeting. The themes are related to (1) the nature of the statistician/nosologist interaction; (2) specific areas of concern in that interaction, and (3) the use of novel and complex statistical methods to challenge and inspire new avenues of thinking among nosologists.

Abstract

Multiple arguments for considering routine dementia screening have been presented. Furthermore, dementia diagnoses are widely unrecognized. As a result, persons with dementia are missing important clinical care and treatment interventions. By distinction, the problems of defining, diagnosing, and treating mild cognitive impairment (MCI) are not yet resolved, and MCI is not ready for a screening recommendation. Dementia screening approaches, including cognitive testing and functional assessment, must be evaluated on their scientific merits, including sensitivity and specificity for recognizing affected individuals in at-risk populations. Screening tests must be "cost-worthy", with the benefits of true-positive test results justifying the costs of testing and resolving false-positive cases, with due consideration for proper diagnostic evaluation and potential harms. With the tremendous number of new cases projected in the near future and the expected emergence of beneficial therapies, considerably more research is needed to develop more efficient screening systems.

Abstract

Popular diets, particularly those low in carbohydrates, have challenged current recommendations advising a low-fat, high-carbohydrate diet for weight loss. Potential benefits and risks have not been tested adequately.To compare 4 weight-loss diets representing a spectrum of low to high carbohydrate intake for effects on weight loss and related metabolic variables.Twelve-month randomized trial conducted in the United States from February 2003 to October 2005 among 311 free-living, overweight/obese (body mass index, 27-40) nondiabetic, premenopausal women.Participants were randomly assigned to follow the Atkins (n = 77), Zone (n = 79), LEARN (n = 79), or Ornish (n = 76) diets and received weekly instruction for 2 months, then an additional 10-month follow-up.Weight loss at 12 months was the primary outcome. Secondary outcomes included lipid profile (low-density lipoprotein, high-density lipoprotein, and non-high-density lipoprotein cholesterol, and triglyceride levels), percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure. Outcomes were assessed at months 0, 2, 6, and 12. The Tukey studentized range test was used to adjust for multiple testing.Weight loss was greater for women in the Atkins diet group compared with the other diet groups at 12 months, and mean 12-month weight loss was significantly different between the Atkins and Zone diets (P

Abstract

Garlic is widely promoted as a cholesterol-lowering agent, but efficacy studies have produced conflicting results. Garlic supplements differ in bioavailability of key phytochemicals. We evaluated the effect of raw garlic and 2 commonly used garlic supplements on cholesterol concentrations in adults with moderate hypercholesterolemia.In this parallel-design trial, 192 adults with low-density lipoprotein cholesterol (LDL-C) concentrations of 130 to 190 mg/dL (3.36-4.91 mmol/L) were randomly assigned to 1 of the following 4 treatment arms: raw garlic, powdered garlic supplement, aged garlic extract supplement, or placebo. Garlic product doses equivalent to an average-sized garlic clove were consumed 6 d/wk for 6 months. The primary study outcome was LDL-C concentration. Fasting plasma lipid concentrations were assessed monthly. Extensive chemical characterization of study materials was conducted throughout the trial.Retention was 87% to 90% in all 4 treatment arms, and chemical stability of study materials was high throughout the trial. There were no statistically significant effects of the 3 forms of garlic on LDL-C concentrations. The 6-month mean (SD) changes in LDL-C concentrations were +0.4 (19.3) mg/dL (+0.01 [0.50] mmol/L), +3.2 (17.2) mg/dL (+0.08 [0.44] mmol/L), +0.2 (17.8) mg/dL (+0.005 [0.46] mmol/L), and -3.9 (16.5) mg/dL (-0.10 [0.43] mmol/L) for raw garlic, powdered supplement, aged extract supplement, and placebo, respectively. There were no statistically significant effects on high-density lipoprotein cholesterol, triglyceride levels, or total cholesterol-high-density lipoprotein cholesterol ratio.None of the forms of garlic used in this study, including raw garlic, when given at an approximate dose of a 4-g clove per day, 6 d/wk for 6 months, had statistically or clinically significant effects on LDL-C or other plasma lipid concentrations in adults with moderate hypercholesterolemia.

Abstract

Thin body preoccupation and social pressure to be thin (TBPSP) in adolescence are risk factors for the development of full and partial bulimia nervosa and binge eating disorder. This study examined precursors of these potent risk factors.A prospective study followed 134 children from birth to 11.0 years and their parents. Recruitment began in January 1990 and ended in March 1991. The study was completed in December 2002.Two moderators identified different groups at risk for the development of TBPSP. A father with high body dissatisfaction characterized the largest group in which TBPSP was elevated for girls who were concerned about and attempted to modify their weight and for children with fathers who had a high drive for thinness. A child at risk for overweight characterized the second smaller group. Parental behaviors such as overcontrol of their child's eating, together with later pressure from parents and peers to be thin, were related to higher levels of TBPSP.Different pathways lead to the development of eating disorder psychopathology. These results suggest that prevention programs for eating disorders should begin in early childhood, possibly involving parental education and behavior change, and that different prevention programs may be required for different pathways.

Abstract

This study examined the impact of telling one's story of childhood sexual abuse and its relationship with the survivor's self-capacities and history of other child maltreatment. The baseline data were collected from 134 female CSA survivors who were participating in a large intervention study. Participants were given 10 minutes to describe their childhood sexual abuse and completed a post-interview questionnaire assessing post-traumatic stress symptoms and their emotional response. The distress in response to their narrative was both predicted and mediated by the survivors' self-capacities and other forms of child maltreatment beyond child sexual abuse.

Abstract

It is our contention that both categorical and dimensional approaches to diagnosis are important for clinical work and research alike, and that each approach has its drawbacks and advantages. As the processes toward developing DSM-V and ICD-11 progress, we suggest that another exclusively categorical revision of psychiatric taxonomies will no longer be sufficient and that adding a dimensional component is a necessary step if these taxonomies are to continue serving the future clinical and research needs of psychiatry as they have so effectively done in the past.We begin the paper with a review of terminology related to categories and dimensions and briefly review literature on advantages and disadvantages of both approaches.A review of relevant literature supports both the need for and feasibility of augmenting traditional categorical diagnoses with dimensional information.We conclude with a proposal for preserving traditional categorical diagnostic definitions, but adding a dimensional component that would be reflective of and directly referable back to the categorical definitions. We also offer a specific proposal for adding a dimensional component to official taxonomies such as the DSM and the ICD in a way that fully preserves the traditional categorical approach.

Abstract

To study how early father involvement and children's biobehavioral sensitivity to social contexts interactively predict mental health symptoms in middle childhood.Fathers' involvement in infant care and maternal symptoms of depression were prospectively ascertained in a community-based study of child health and development in Madison and Milwaukee, WI. In a subsample of 120 children, behavioral, autonomic, and adrenocortical reactivity to standardized challenges were measured as indicators of biobehavioral sensitivity to social context during a 4-hour home assessment in 1998, when the children were 7 years of age. Mental health symptoms were evaluated at age 9 years using parent, child, and teacher reports.Early father involvement and children's biobehavioral sensitivity to context significantly and interactively predicted symptom severity. Among children experiencing low father involvement in infancy, behavioral, autonomic, and adrenocortical reactivity became risk factors for later mental health symptoms. The highest symptom severity scores were found for children with high autonomic reactivity that, as infants, had experienced low father involvement and mothers with symptoms of depression.Among children experiencing minimal paternal caretaking in infancy, heightened biobehavioral sensitivity to social contexts may be an important predisposing factor for the emergence of mental health symptoms in middle childhood. Such predispositions may be exacerbated by the presence of maternal depression.

Abstract

Exploratory studies that generate testable models of how risk factors for childhood mental health problems work together over time are critical for developing effective prevention and treatment strategies.To build models addressing the following 2 questions: (1) How early can we identify children at risk for mental health problems in third grade? (2) How do the risk factors work together over time?We assessed a Wisconsin community sample 8 times, beginning during pregnancy. Three hundred seventy-nine families completed multi-informant reports (mothers, teachers, and children) of children's mental health symptoms in third grade.Symptom severity and directionality (externalizing vs internalizing).The hypothesis was generated that family socioeconomic status (SES) defined different pathways to symptom severity. In low/middle SES families, children were at risk if their mothers were distressed during the infancy period, which was then associated with more generalized maternal and child distress and dysregulation during the preschool period. In high SES families, the picture was more complex, beginning with parental histories of depression and family psychopathology, which then led to greater family stress in the infancy period and maternal and child distress and dysregulation during the preschool period. For all children, social and academic impairment during the school transition was an important mediator. Two pathways to later symptom directionality consisted of one beginning with child sex and the other with child temperament.Most risk factors predicted symptom severity and not directionality. The risk factors for internalizing and externalizing problems may be much the same, and the same preventive interventions might be effective for both classes of problems. Furthermore, at-risk children from high SES families might be identifiable as early as infancy, whereas those from lower SES families may be identifiable only as preschoolers.

Abstract

The normal diurnal cortisol cycle has a peak in the morning, decreasing rapidly over the day, with low levels during the night, then rising rapidly again to the morning peak. A pattern of flatter daytime slopes has been associated with more rapid cancer progression in both animals and humans. We studied the relationship between the daytime slopes and other daytime cortisol responses to both pharmacological and psychosocial challenges of hypothalamic-pituitary-adrenal (HPA) axis function as well as DHEA in a sample of 99 women with metastatic breast cancer, in hopes of elucidating the dysregulatory process. We found that the different components of HPA regulation: the daytime cortisol slope, the rise in cortisol from waking to 30 min later, and cortisol response to various challenges, including dexamethasone (DEX) suppression, corticotrophin releasing factor (CRF) activation, and the Trier Social Stress Task, were at best modestly associated. Escape from suppression stimulated by 1mg of DEX administered the night before was moderately but significantly associated with flatter daytime cortisol slopes (r=0.28 to .30 at different times of the post DEX administration day, all p

Abstract

The objectives of this study were to evaluate the magnitude and sources of site differences in a multisite study of rates of cognitive decline among patients with Alzheimer disease and to seek strategies to reduce the magnitude of site differences in this and future such studies.A total of 3,280 participants from 15 different sites was analyzed. For each participant, the average rate of change in the Mini-Mental State Examination (MMSE) was calculated. Participants who declined at least three MMSE points per year were classified "rapid decliners." Site differences in sociodemographic distributions and the percentage of rapid decliners were examined, and a signal detection approach was used to identify the main correlates of rapid decline.The percentage of rapid decliners for the 15 sites initially varied from 8%-40%. Two of the correlates of rapid decline were largely the result of different sampling protocols, namely baseline MMSE and elapsed time between the first and last MMSE. By selecting only those participants at each site with a baseline MMSE between 15 and 23, and limiting the follow-up time to a period of 11-24 months, the authors created greater homogeneity in the protocols across sites and reduced site variability of rapid decliners from 27%-50%.Results of single-site studies are often nonreproducible, and multisite studies that follow different protocols and do not take site differences into account may be misleading. This study indicates the importance of site differences and how relatively simple efforts to impose common sampling, measurement, and design criteria can reduce, if not totally remove, site differences.

Abstract

Little is known about how deeply medication treatment penetrates different levels of the mind/brain system. Psychopathology consists of relatively simple constructs (e.g., anger, irritability), or complex ones (e.g., responsibility). This study examines the efficacy of a specific compound, divalproex sodium (DVPX), on the various levels of psychopathology, utilizing a previous study in which 71 youth with conduct disorder were enrolled in a randomized controlled 7-week clinical trial. We examined weekly slopes of "emotional cognitions" of varying degrees of complexity obtained by Weinberger Adjustment Inventory (WAI), measuring more basic states, such as anger, depression, happiness and anxiety, and complex states, such as impulse control, consideration of others, responsibility and self-esteem. Intent-to-treat analyses showed significant associations between assignment to the active treatment and improvement in depression and impulse control. This is a rare clinical trial, which provides preliminary evidence for the different profiles of efficacy of medication treatment.

Abstract

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

Abstract

The National Heart, Lung, and Blood Institute convened an interdisciplinary working group of experts to develop recommendations for the assessment and treatment of depression in patients with coronary heart disease (CHD).Consensus of experts.Our current recommendations are that the Beck Depression Inventory-I be employed for epidemiological studies of depression and CHD, that the Patient Health Questionnaire 2-item version be employed for screening for trial eligibility, that the Depression Interview and Structured Hamilton (DISH) be employed for diagnostic ascertainment for trial inclusion, and that the Hamilton rating scale, which is part of the DISH, be employed for both depression symptom reduction and the remission criterion in any trial. We further recommend that a randomized controlled trial be undertaken to determine whether selective serotonin reuptake inhibitors, psychotherapy, or combined treatment can reduce the risk of CHD events and mortality associated with depression in CHD patients.This report summarizes the recommendations made by the working group and discusses the rationale for each recommendation, the strengths and weaknesses of alternative approaches to assessment and treatment, and the implications for future research in this area.

Abstract

Cancer-related distress due to the psychological and physical challenges of metastatic breast cancer (MBC) may result in symptoms of depression, which negatively affects quality and may influence quantity of life. This study investigated how depression affects MBC stress reactivity, including autonomic (ANS) and hypothalamic-pituitary-adrenal (HPA) axis function.Forty-five nondepressed and 45 depressed patients with MBC underwent a modified Trier Social Stress Test (TSST) while affect, cardiovascular, respiratory, and cortisol responses were measured.At study entry, depressed compared with nondepressed patients had significantly lower log cortisol waking rise levels (p = .005) but no other HPA differences. Positive affect (p = .025) and high-frequency heart-rate variability (lnHF) (p = .002) were significantly lower at TSST baseline in depressed patients. In response to the TSST, depressed patients reported significantly lower positive (p = .050) and greater negative affect (p = .037) and had significantly reduced lnHF (p = .031). In secondary analyses, at TSST baseline both low-frequency (lnLF) (p = .002) and very-low-frequency (lnVLF) (p = .0001) heart rate variability were significantly lower in the depressed group. In secondary analyses during the TSST, those who were depressed had significantly lower lnVLF (p = .008) and did not increase aortic impedance reactivity as much as did the nondepressed during the stressor (p = .005).Depression in patients with MBC was associated with alterations in autonomic regulation, particularly reductions in respiratory sinus arrhythmia, a measure of cardiac vagal control, at baseline and during the TSST. In addition, depression was associated with blunted HPA response to awakening. Both MBC groups had relative cortisol hyporesponsiveness to acute stress.

Abstract

In randomized clinical trails (RCTs), effect sizes seen in earlier studies guide both the choice of the effect size that sets the appropriate threshold of clinical significance and the rationale to believe that the true effect size is above that threshold worth pursuing in an RCT. That threshold is used to determine the necessary sample size for the proposed RCT. Once the RCT is done, the data generated are used to estimate the true effect size and its confidence interval. Clinical significance is assessed by comparing the true effect size to the threshold effect size. In subsequent meta-analysis, this effect size is combined with others, ultimately to determine whether treatment (T) is clinically significantly better than control (C). Thus, effect sizes play an important role both in designing RCTs and in interpreting their results; but specifically which effect size? We review the principles of statistical significance, power, and meta-analysis, and commonly used effect sizes. The commonly used effect sizes are limited in conveying clinical significance. We recommend three equivalent effect sizes: number needed to treat, area under the receiver operating characteristic curve comparing T and C responses, and success rate difference, chosen specifically to convey clinical significance.

Abstract

Comorbidity is the rule rather than the exception with psychiatric disorders and is consequently of great interest to both researchers and clinicians. However, many studies of psychiatric comorbidity have been based on lifetime prevalence with mixed-age samples, a practice that (1) biases the assessment of epidemiologic comorbidity and (2) creates the appearance of comorbidity even when disorders are randomly associated. This bias is what we refer to as pseudocomorbidity.To clarify the source of the problem and to discuss strategies that might be adopted to deal hereafter with lifetime prevalence data.A simulated example is presented to show that even when there is only random association between disorders, there will appear to be nonrandom comorbidity when lifetime prevalence is used with mixed-age samples. An actual example relating psychosis to phobia is presented to show the bias that can result and to illustrate one way of dealing with lifetime prevalence data.Use of lifetime prevalence with mixed-age samples, used almost exclusively in psychiatric research, generates problematic results, especially when used for assessment of comorbidity, and should be viewed with some skepticism. Hereafter, we recommend that any future use of lifetime prevalence should require determination of the age of onset, even if only by retrospective report. Comorbidity then should be reported by age.

Abstract

The objective was to determine risk factors of psychiatric hospitalization among a Veterans Administration database of patients with dementia and comorbid bipolar disorder (D+BD). Patients with D+BD had a greater prevalence of psychiatric hospitalization (28% vs 4%). The strongest predictor of psychiatric hospitalization was the presence of an alcohol use disorder (51% risk); patients without alcohol use disorders but under the age of 70 had the next highest risk (33% risk). However, patients with an alcohol use disorder had shorter psychiatric hospitalizations than those without. Compared with patients without BD, D+BD patients were more likely to have alcohol use disorders (15% vs 3%) and any other substance use problem (10% vs 1%). In patients diagnosed with dementia and bipolar disorder, the strongest risk factor for psychiatric hospitalization was an alcohol abuse disorder. These findings suggest that disorders with increased frequency in BD affect the course of dementia.

Abstract

Clinical researchers often propose (or review committees demand) pilot studies to determine whether a study is worth performing and to guide power calculations. The most likely outcomes are that (1) studies worth performing are aborted and (2) studies that are not aborted are underpowered. There are many excellent reasons for performing pilot studies. The argument herein is not meant to discourage clinical researchers from performing pilot studies (or review committees from requiring them) but simply to caution against their use for the objective of guiding power calculations.

Abstract

This study examined differences in psychologic and physiological responses to caregiving stress in Hispanic and non-Hispanic white women dementia caregivers and noncaregivers. Dependent variables were perceived stress, depression, and salivary cortisol.Eighty-three women caregivers (20 Hispanic and 24 non-Hispanic white) and noncaregivers (19 Hispanic and 20 non-Hispanic white) completed the Perceived Stress Scale (PSS), Center for Epidemiological Studies-Depression Scale (CES-D), and collected three saliva samples daily for 3 consecutive days. A subsample of 17 Hispanic and 28 non-Hispanic white participants matched on age and education was used for the main analyses.Caregivers had higher levels of 8 am, 5 pm, and 9 pm log cortisol as well as higher perceived stress than noncaregivers. Non-Hispanic whites had higher depression scores than noncaregivers, but there was no significant difference for Hispanics. Hispanics, regardless of caregiving status had flatter daytime cortisol slopes than the non-Hispanic whites. Multivariate regression analyses showed that both ethnicity and depressive symptoms independently predicted daytime cortisol slope.Results support the relationship between chronic stress and hypothalamic-pituitary-adrenal axis dysregulation among women dementia caregivers and highlight the need to examine further the role of ethnicity and depressive symptoms in their physiological responses.

Abstract

The daytime log-cortisol slope appears to be of growing importance in studying the relationship between stress and health. How best to estimate that slope with minimal burden to the participants and the cost of the study is a decision often made without empiric foundation.In 50 older participants, the authors examined cortisol assay comparability across laboratories, assay reliability, test-retest reliability of slopes, and comparability of slope estimates for two, three, and four samples per day.The authors demonstrate in an older sample that 1) assay reliability is a relatively minor issue, that one assay per saliva sample suffices; 2) the use of a sample obtained at wake time for each participant appears to be a preferred anchor for the slope estimate in comparison to a sample 30 minutes postwake time; 3) self-reported times appear preferable to automatic time recording; and 4) test-retest reliability of slopes, however, is not sufficiently high to base a slope estimate on one day; minimally two days and preferably three should be required.Whether these conclusions apply to other populations, or using other protocols, is not assured, but the study itself provides a model that can be used to check research decisions. Unnecessarily imposing a burdensome protocol has both ethical and scientific ramifications and should be carefully avoided.

Abstract

The question of whether to screen for dementia and Alzheimer's disease (AD) has been discussed in many forums throughout the world. Generally, medical advisory groups and policy-making groups have recognized the importance of early diagnosis but have uniformly avoided making recommendations to screen at-risk populations. This presentation reflects the support for reconsidering the importance of screening individuals at risk or above a certain age. In this statement, the majority of the authors support the consideration of dementia risk factors in individuals at age 50, with routine yearly screening after 75. Other authors remain concerned that the benefits of treatments of early disease do not yet support a general screening recommendation. These statements are made to encourage progress toward the development of a consensus regarding the widespread institution of screening policy. Accordingly, members of the worldwide scientific community are invited to add their perspective by contributing short commentaries (1500 words) on this subject.

Abstract

The objectives of this study were to provide estimates of the prevalence and strength of association between major depression and chronic pain in a primary care population and to examine the clinical burden associated with the two conditions, singly and together.A random sample of Kaiser Permanente patients who visited a primary care clinic was mailed a questionnaire assessing major depressive disorder (MDD), chronic pain, pain-related disability, somatic symptom severity, panic disorder, other anxiety, probable alcohol abuse, and health-related quality of life (HRQL). Instruments included the Patient Health Questionnaire, SF-8, and Graded Chronic Pain Questionnaire. A total of 5808 patients responded (54% of those eligible to participate).Among those with MDD, a significantly higher proportion reported chronic (i.e., nondisabling or disabling) pain than those without MDD (66% versus 43%, respectively). Disabling chronic pain was present in 41% of those with MDD versus 10% of those without MDD. Respondents with comorbid depression and disabling chronic pain had significantly poorer HRQL, greater somatic symptom severity, and higher prevalence of panic disorder than other respondents. The prevalence of probable alcohol abuse/dependence was significantly higher among persons with MDD compared with individuals without MDD regardless of pain or disability level. Compared with participants without MDD, the prevalence of other anxiety among those with MDD was more than sixfold greater regardless of pain or disability level.Chronic pain is common among those with MDD. Comorbid MDD and disabling chronic pain are associated with greater clinical burden than MDD alone.

Abstract

Off-label prescribing of medications, polypharmacy, and other questionable prescribing practices have led investigators to examine a large VA pharmacy database to determine if physician prescribing decisions appear reasonable.The current study addresses the question of physician prescribing of atypical antipsychotics in 34,925 veterans with schizophrenia, using a series of signal detection analyses.These results suggest that only three factors (hospital size, age, and secondary diagnosis) allow classification of patients prescribed atypicals into three groups with frequencies of use of atypicals ranging from 43% to 79%, and that these results are consistent with reasonable clinical practice.Results of two-stage signal detection analyses are readily interpretable by clinicians and administrators who are faced with the task of evaluating how physicians prescribe medications in clinical practice. Physicians' decisions to prescribe atypical antipsychotics are based on both patient and fiscal considerations. This likely reflects a combination of clinical judgment and institutional guidelines.

Abstract

The current study used Department of Veteran's Affairs (VA) clinical records, State of California pesticide application records, spatial maps of distribution of Parkinson's disease patients, and pesticide applications to determine if there was evidence for "blow-in" of pesticides as a factor in explaining the prevalence of Central Valley Parkinson's disease. The results did not support the hypothesis of increasing prevalence of Parkinsonism attributable to wind drift.

Abstract

To examine the prevalence and correlates of night eating, the core behavioral symptom of night eating syndrome among adolescents and adults, using two public access survey databases of nationally representative samples.Data were extracted for individuals age 13 years or older who completed food diary data for the National Health and Nutrition Examination Survey III (N = 18,407) or the Continuing Survey of Food Intakes by Individuals (N = 10,741). Prevalence estimates were calculated for three commonly used definitions of night eating. Logistic regression was used to examine correlates of night eating: type of day, season, gender, age, race/ethnicity, and BMI or obesity.With few exceptions, findings were similar in the two surveys. Night eating is most common during the weekend; prevalence is greatest among young adults (18 to 30 years of age) and least common among individuals age 65 years or older; and is not associated with BMI or obesity. Gender or ethnicity effects were not found to be stable across surveys.Experts need to consider type of day, age group, and possibly gender and race/ethnicity when examining population differences in night eating. Longitudinal studies are needed to further examine the link between night eating and obesity.

Abstract

Presentation of effect sizes that can be interpreted in terms of clinical or practical significance is currently urged whenever statistical significance (a 'p-value') is reported in research journals. However, which effect size and how to interpret it are not yet clearly delineated. The present focus is on effect sizes indicating strength of correlation, that is, effect sizes that describe the strength of monotonic association between two random variables X and Y in a population.A logical structure of measures of association is traced, showing the interrelationships among the many measures of association. Advantages and disadvantages of each are discussed.Suggestions are made for the future use of measures of association in research to facilitate considerations of clinical significance, emphasizing distribution-free effect sizes such as the Spearman correlation coefficient and Kendall's coefficient of concordance for ordinal versus ordinal associations, weighted and intraclass kappa for binary versus binary associations and risk difference (RD) for binary versus ordinal association.

Abstract

This study examined evidence for a dissociative subtype of post-traumatic stress disorder (PTSD) among women seeking psychotherapy for childhood sexual abuse (CSA). One hundred and twenty-two women seeking treatment for CSA completed a battery of questionnaires assessing PTSD, dissociative symptoms, and child maltreatment. Using signal detection analysis, we identified high and low dissociation PTSD subgroups. A constellation of three PTSD symptoms-hypervigilance, sense of foreshortened future, and sleep difficulties-discriminated between these two subgroups (OR = 8.15). Further evidence was provided by the finding of a nonlinear relationship between severity of childhood maltreatment and dissociation in the women with PTSD. These results provide support for a dissociative subtype of PTSD that may stem from more severe childhood experiences of neglect and abuse.

Abstract

Natural killer (NK) cells are a class of lymphocytes important in immune resistance to viral and other serious diseases. The cytotoxic function, or 'killing activity' of NK cells has become important in studies of the effects of stress and other psychosocial factors on physical health. Unfortunately, research on NK cell function has been plagued by discrepancies in the methods of interpreting NK cytotoxicity data. We briefly review some of the variations in measuring NK cell activity and present a new model for interpreting these results, introducing maximal target cell lysis (A) and the slope of the cytolytic curve (k) as parameters that attempt to make full use of the information and the statistical power in NK cell cytotoxicity data. Examples of these interpretation methods are presented using NK cytotoxicity data from a group of metastatic breast cancer patients. This approach will be useful in applications of NK cell measurement in psychoneuroimmunology research.

Abstract

The prevalence of depressive symptoms from adolescence through young adulthood was examined in 1,146 African-American adolescent girls and 1,075 Caucasian adolescent girls who completed the Center for Epidemiological Studies of Depression scale. Caucasian girls' scores decreased over time, whereas scores for African-American girls were fairly consistent. Future studies are needed to examine age-specific risk factors in adolescent girls.

Abstract

R. Rosenthal and D. B. Rubin (2003) proposed an effect size, r equivalent, to be used when (a) only sample size and p values are known for a study, (b) there are no generally accepted effect size indicators, or (c) sample sizes are so small or the data so non-normal that the directly computed effect sizes would be more misleading than the simple effect size. The limitations of their proposal, however, are many, and much more serious than the authors suggested, and should be carefully considered before this effect size is applied, as well as in developing other effect sizes using similar methods.

Abstract

Depression in adolescent girls may result in negative consequences in young adulthood. The Center for Epidemiologic Studies Depression Scale (CES-D) was administered to 1,727 Black and White girls ages 16 to 18 years who participated in the National Heart, Lung, and Blood Institute's Growth and Health Study. Three years later, women in the depressed groups were more likely to be current smokers, had attained a lower level of education, and reported lower self-worth relative to the nondepressed group. Body dissatisfaction, eating concerns, and loneliness were greater in the depressed groups. Relative to Black women, White women who were moderately depressed during adolescence reported more health care services utilization in young adulthood. Prevention efforts for depressed adolescents should be broadly focused to improve young adult outcomes.

Abstract

Screening strategies play an important part in the identification and diagnosis of illness. Testing of such strategies in a clinical trial can have important implications for the treatment of such illnesses. Before the clinical trial, however, it is important to develop a practical screening/classification procedure that accurately predicts the presence of the illness in question. Recent published studies have shown a growing preference for classification tree/recursive partitioning procedures.This paper compares the application of logistic regression and recursive partitioning to a neuropsychological data set of 252 patients recruited from four Veterans Affairs Medical Centers. Logistic regression and recursive partitioning was used to predict cognitive impairment in 12 randomly selected exploratory/validation samples. We assessed the effect of sampling on variable selection and predictive accuracy.Predictive accuracy of the logistic regression and recursive partitioning procedures was comparable across the exploratory data samples but varied across the validation samples. Based on shrinkage, both classification procedures performed equally well for the prediction of cognitive impairment across the twelve samples. While logistic regression provided an estimated probability of outcome for each patient, it required several mathematical calculations to do so. However, logistic regression selected one or two less predictors than recursive partitioning with comparable predictive accuracy. Recursive partitioning, on the other hand, readily identified patient characteristics and variable interactions, was easy to interpret clinically and required no mathematical calculations. There was a high degree of overlap of the predictor variables between the two procedures.In the context of neuropsychological screening, logistic regression and recursive partitioning performed equally well and were quite stable in the selection of predictors for the identification of patients with cognitive impairment, although recursive partitioning may be easier to use in a clinical setting because it is based on a simple decision tree.

Abstract

Multicenter studies involving randomized clinical trials (RCTs) may have different structures. We discuss four general types. The first two, an "ideal" multicenter RCT and decentralized multicenter collaborative RCTs, we feel are, in different circumstances, highly recommended approaches. The other two, the multicenter RCT that ignores site differences and centralized multicenter collaborative RCTs, we argue, are not only not cost-effective but may also produce misleading results, thus impeding scientific progress and possibly putting patients at unnecessary risk.

Abstract

The authors investigated the relationship between obstructive sleep apnea/hypopnea (OSAH) and cognition in 36 older adults, 18 APOE epsilon4 carriers, and 18 non-carriers. Greater numbers of respiratory events negatively impacted memory function in epsilon4 carriers only. This is the first study to provide preliminary evidence for a negative interaction of APOE epsilon4 and OSAH on memory in older adults, which may have important implications for treating cognitive decline and delaying dementia onset.

Abstract

This descriptive study examined reports of behavioral problems among older patients hospitalized in acute care medical settings. Greater numbers of behavioral problems were reported by nursing staff on the Neuropsychiatric Inventory-Questionnaire than were documented in medical charts over the same time period. Such underreporting may have clinical and administrative implications.

A comparison of short- and long-term family therapy for adolescent anorexia nervosaJOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRYLock, J., Agras, W. S., Bryson, S., Kraemer, H. C.2005; 44 (7): 632-639

Abstract

Research suggests that family treatment for adolescents with anorexia nervosa may be effective. This study was designed to determine the optimal length of such family therapy.Eighty-six adolescents (12-18 years of age) diagnosed with anorexia nervosa were allocated at random to either a short-term (10 sessions over 6 months) or long-term treatment (20 sessions over 12 months) and evaluated at the end of 1 year using the Eating Disorder Examination (EDE) between 1999 and 2002.Although adequately powered to detect differences between treatment groups, an intent-to-treat analysis found no significant differences between the short-term and long-term treatment groups. Although a nonsignificant finding does not prove the null hypothesis, in no instance does the confidence interval on the effect size on the difference between the groups approach a moderate .5 level. However, post hoc analyses suggest that subjects with severe eating-related obsessive-compulsive features or who come from nonintact families respond better to long-term treatment.A short-term course of family therapy appears to be as effective as a long-term course for adolescents with short-duration anorexia nervosa. However, there is a suggestion that those with more severe eating-related obsessive-compulsive thinking and nonintact families benefit from longer treatment.

Abstract

There have been very few randomized controlled treatment studies of anorexia nervosa.To evaluate factors leading to nonacceptance and noncompletion of treatment for 2 specific therapies and their combination in the treatment of anorexia nervosa.Randomized prospective study.Weill-Cornell Medical Center, White Plains, NY; University of Minnesota, Minneapolis; and Stanford University, Stanford, Calif. Patients One hundred twenty-two patients meeting DSM-IV criteria for anorexia nervosa.Treatment with cognitive-behavioral therapy, fluoxetine hydrochloride, or their combination for 1 year.Dropout rate and acceptance of treatment (defined as staying in treatment at least 5 weeks).Of the 122 randomized cases, 21 (17%) were withdrawn; the overall dropout rate was 46% (56/122) in the remaining patients. Treatment acceptance occurred in 89 (73%) of the 122 randomized cases. Of the 41 assigned to medication alone, acceptance occurred in 23 (56%). In the other 2 groups, acceptance rate was differentiated by high and low obsessive preoccupation scores (rates of 91% and 60%, respectively). The only predictor of treatment completion was high self-esteem, which was associated with a 51% rate of treatment acceptance.Acceptance of treatment and relatively high dropout rates pose a major problem for research in the treatment of anorexia nervosa. Differing characteristics predict dropout rates and acceptance, which need to be carefully studied before comparative treatment trials are conducted.

Abstract

Participants included 165 children with attention-deficit/hyperactivity disorder (ADHD; 130 boys, 35 girls) and their 1,298 same-sex classmates (1,026 boys, 272 girls) who served as raters. For each child with ADHD, a child of the same sex was randomly selected from the same classroom to serve as a comparison child, which yielded 165 dyads. Consistent with predictions, contrasted with the comparison children, those with ADHD were lower on social preference, higher on social impact, less well liked, and more often in the rejected social status category; they also had fewer dyadic friends. When liking ratings that children made versus received were examined, children with ADHD had less positive imbalance and greater negative imbalance relative to comparison children. Analyses that considered the types of peers who chose children with ADHD as friends or nonfriends demonstrated that children with ADHD were nominated as nonfriends by children of higher social preference and who were better liked by others.

Abstract

This study sought to identify in white women risk factors specific to binge-eating disorder (BED) and for psychiatric disorders in general, and to compare black and white women on risk factors for BED.A case-control design was used. Participants were recruited from the community and included 162 women who met DSM-IV criteria for BED and two comparison groups of women with no history of clinically significant eating disorder symptoms. The comparison women were matched to BED women on age, education and ethnicity and divided into a healthy comparison (HC) group, who had no current psychiatric disorder, and a psychiatric comparison (PC) group, who had a diagnosis of a DSM-IV Axis I psychiatric disorder. The study sample size was determined by the group with the least members (PC), including 107 women with BED and 214 matched comparison women. A broad range of risk factors was assessed with a Risk Factor Interview and the Parental Bonding Instrument.No significant effects for ethnicity by diagnostic group were found. BED women reported higher exposure to childhood obesity, family overeating or binge-eating, family discord, and high parental demands than PC women. The combined BED and PC group scored significantly higher than the HC group on measures of negative affect, parental mood and substance disorders, perfectionism, separation from parents, and maternal problems with parenting.These findings indicate that childhood obesity and familial eating problems are reliable specific risk factors for BED. Ethnicity does not appear to moderate risk for BED.

Abstract

Oxybutynin is a powerful anticholinergic drug already known to impair cognition in the elderly. The impact of this drug on cognitive functioning in the pediatric population is unknown. We report the results of a study designed to assess the effect of oxybutynin on cognitive function in children.A total of 25 patients presenting with the primary symptom of daytime enuresis were recruited for this nonrandomized trial. All subjects initially received 4 weeks of behavior modification, followed by an additional 4 weeks of behavior modification either alone or with oxybutynin for continued treatment of enuresis. Neuropsychological testing was performed at baseline (4 weeks) and after additional therapy (8 weeks).Patient demographics included a male-to-female ratio of 11:14 and a mean age of 7.2 +/- 1.8 years. A total of 10 patients were assigned to the control group receiving behavior modification, and 15 patients were assigned to the treatment group receiving behavior modification plus oxybutynin. The oxybutynin treated patients had a lower overall performance at baseline pretreatment testing. However, performance in this group improved following treatment with oxybutynin.Oxybutynin, a commonly used pharmacological agent in pediatric urology, was not associated with cognitive impairment following treatment. However, we observed lower baseline cognitive functioning in patients whose parents chose oxybutynin over behavior modification alone. This finding may represent a selection bias. However, it also supports the need for a multidisciplinary approach to the treatment of patients with dysfunctional voiding, as some may have cognitive difficulties that have not previously been explored.

Abstract

To explore heart rate (HR) correlates of attachment behavior in young mothers and their infants to generate specific hypotheses and to provide pilot data on which studies to test those hypotheses might be based.Using the strange situation procedure, patterns of attachment were assessed in 41 low-income adolescent mothers and their infants. During the procedure, the HRs of the infants and mothers were recorded. The HR changes were analyzed and infant attachment group differences were examined.Infants in all attachment groups demonstrated a similar HR response. There were, however, notably different behavioral reactions in the insecure groups: relatively increased behavioral distress in the insecure/resistant infants and relatively decreased behavioral distress in insecure-avoidant infants. Mothers of insecure-resistant infants demonstrated elevated HRs during reunions and the insecure/resistant dyads demonstrated lower consistency between HR changes in infant and mother than the secure dyads.The results suggest the discrepancy between attachment-related behavioral reactions and HR response in insecurely attached infants. Maternal and dyadic HR changes vary between the attachment groups.

Abstract

This study reports the prevalence and comorbidity of depression in two large samples of black and white young adult women.Clinical interviews of participants in a follow-up study of the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS-Wave II; N=378) were contrasted with a subsample of the National Comorbidity Survey (NCS; N=3749) to examine the rates and comorbidity of lifetime major depressive disorder in black and white women using methodology described by . The sequencing of disorders was also examined to determine which disorder was primary. Comorbidity and sequencing were examined for alcohol and drug use disorder, panic disorder, specific phobia, social phobia, and post-traumatic stress disorder.Prevalence estimates for depression, alcohol use disorder, and drug use disorder were higher for white women than for black women in both NGHS-Wave II and NCS. Over half of depressed participants in both samples had at least one comorbid disorder and depression was associated with an increased probability of all the investigated disorders. Only one ethnic difference was found in comorbidity, indicating that black women were more likely to have comorbid panic disorder than white women were. Depression was primary to alcohol and substance use disorders, whereas it was secondary to specific phobia and PTSD.High rates of comorbidity were found for both black and white women, though few ethnic differences in comorbidity were found. Preventive and treatment interventions are needed to address multiple disorders in young adult women.

Abstract

Peer-assessed outcomes were examined at the end of treatment (14 months after study entry) for 285 children (226 boys, 59 girls) with attention deficit hyperactivity disorder (ADHD) who were rated by their classmates (2,232 classmates total) using peer sociometric procedures. All children with ADHD were participants in the Multimodal Treatment Study of Children with ADHD (MTA). Treatment groups were compared using the orthogonal treatment contrasts that accounted for the largest amount of variance in prior MTA outcome analyses: Medication Management + Combined Treatment versus Behavior Therapy + Community Care; Medication Management versus Combined Treatment; Behavior Therapy versus Community Care. There was little evidence of superiority of any of the treatments for the peer-assessed outcomes studied, although the limited evidence that emerged favored treatments involving medication management. Post hoc analyses were used to examine whether any of the four treatment groups yielded normalized peer relationships relative to randomly selected-classmates. Results indicated that children from all groups remained significantly impaired in their peer relationships.

Abstract

Patients often experience 'preparatory-grief' as they cope with the dying process. Some may be depressed. The Terminally Ill Grief or Depression Scale (TIGDS), comprising grief and depression sub-scales, is a new self-report measure designed to differentiate between preparatory-grief and depression in adult inpatients. The initial 100-item inventory was assembled based on literature review, interviews with clinicians and dying patients and then shortened to 42 items based on consensus expert opinion. Validity and reliability were tested in a sample of 55 terminally ill adults. The consensus clinical opinion was used as the gold standard to differentiate between preparatory grief and depression. The intra-class correlation coefficient was high (it was calculated to estimate the test-retest reliability for the 47 patients who had completed the TIGDS twice--retest was administered 2 to 7 days after the initial test), ranging from 0.86 (grief) to 0.97 (depression). The validity of TIGDS was assessed using a receiver operating characteristic curve analysis, comparing the first test with the clinical criterion. The first and only variable and cut-point was the depression score (chi-square = 18.4, p < 0.001, cut point = 3). The sensitivity of the TIGDS was 0.727 and specificity was 0.886 for the depression = 3 cutoff score. The construct validity of the TIGDS was tested by comparing with the Hospital Anxiety and Depression Scale (HADS). The TIGDS depression subscale showed strong convergent validity and the TIGDS grief subscale showed strong discriminant validity with the HADS total score.

Abstract

The current study examined health services use during the past 12 months in a sample of young women with a history of an adolescent eating disorder (bulimia nervosa [BN] or binge eating disorder [BED]).A community sample of 1,582 young women (mean age = 21.5 years) was classified, based on a screening interview (and, for eating disorder diagnosis, confirmatory diagnostic interview), into one of three groups: BN or BED (n = 67), other psychiatric disorder (n = 443), and no adolescent psychiatric disorder (n = 1,072).A history of BN/BED in adolescence was associated with elevated health services use, but this was a general effect associated with having a psychiatric disorder, not an effect specific to the diagnosis of an eating disorder. Total service days, outpatient psychotherapy visits, and emergency department visits were elevated in the combined group of BN/BED and other psychiatric disorder participants relative to the healthy comparison group. The women with BN/BED did not differ significantly from the women with a non-eating-related psychiatric disorder in the use of these services.The similarity of health services use in young women with BN or BED and those with other psychiatric disorders underscores the clinical and economic impact of these eating disorders.

Abstract

Nurse care management programs for patients with chronic illness have been shown to be safe and effective.To determine whether a telephone-mediated nurse care management program for heart failure reduced the rate of rehospitalization for heart failure and for all causes over a 1-year period.Randomized, controlled trial of usual care with nurse management versus usual care alone in patients hospitalized for heart failure from May 1998 through October 2001.5 northern California hospitals in a large health maintenance organization.Of 2786 patients screened, 462 met clinical criteria for heart failure and were randomly assigned (228 to intervention and 234 to usual care).Nurse care management provided structured telephone surveillance and treatment for heart failure and coordination of patients' care with primary care physicians.Time to first rehospitalization for heart failure or for any cause and time to a combined end point of first rehospitalization, emergency department visit, or death.At 1 year, half of the patients had been rehospitalized at least once and 11% had died. Only one third of rehospitalizations were for heart failure. The rate of first rehospitalization for heart failure was similar in both groups (proportional hazard, 0.85 [95% CI, 0.46 to 1.57]). The rate of all-cause rehospitalization was similar (proportional hazard, 0.98 [CI, 0.76 to 1.27]).The findings of this study, conducted in a single health care system, may not be generalizable to other health care systems. The overall effect of the intervention was minor.Among patients with heart failure at low risk on the basis of sociodemographic and medical attributes, nurse care management did not statistically significantly reduce rehospitalizations for heart failure or for any cause. Such programs may be less effective for patients at low risk than those at high risk.

Abstract

Television viewing has been associated with childhood obesity, although the mechanisms that link television viewing to higher BMI have not been established. Therefore, our objectives, in this report, were to describe the amount and types of foods that African-American girls consume while watching television and to examine the associations between African-American girls' BMI and the food they consume while watching television.Data were collected from 210 8- to 10-year-old African-American girls at four field centers by trained and certified nutritionists. Two nonconsecutive 24-hour dietary recalls were collected from each girl. For each eating episode reported, the girls were asked if they had been watching television while eating. Height and weight were collected using standard methods and used to calculate BMI.The data were analyzed separately by field center. The proportion of average daily energy intake that the girls consumed while watching television ranged from 26.9% to 35.0%. At all field centers, 40% to 50% of evening meals were consumed while watching television. None of the Spearman correlations between girls' BMI and the amount and type of foods consumed while watching television or at other times during the day were statistically significant (p > 0.05).This research revealed that a significant proportion of African-American girls' daily energy intake is consumed while watching television. Interventions that target reductions in food consumption while watching television or reducing television viewing may be effective strategies to decrease children's energy intakes. These results support a need for research to test the efficacy of these approaches.

Abstract

To stimulate the development of new drugs for the cognitive deficits of schizophrenia, the National Institute of Mental Health (NIMH) established the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. This article presents an overview of decisions from the first MATRICS consensus conference. The goals of the meeting were to 1) identify the cognitive domains that should be represented in a consensus cognitive battery and 2) prioritize key criteria for selection of tests for the battery. Seven cognitive domains were selected based on a review of the literature and input from experts: working memory, attention/vigilance, verbal learning and memory, visual learning and memory, reasoning and problem solving, speed of processing, and social cognition. Based on discussions at this meeting, five criteria were considered essential for test selection: good test-retest reliability, high utility as a repeated measure, relationship to functional outcome, potential response to pharmacologic agents, and practicality/tolerability. The results from this meeting constitute the initial steps for reaching a consensus cognitive battery for clinical trials in schizophrenia.

Abstract

To compare rates of institutionalization of dementia patients cared for by Latina and Caucasian female caregivers and to explore which caregiver and care-recipient characteristics predicted institutionalization.Longitudinal.San Francisco Bay area, California.Two hundred sixty-four female caregivers of dementia patients (154 Caucasian women, 110 Latinas) who participated in an intervention project designed to reduce caregiver stress and may represent a sample that is more stressed and motivated than a general sample of caregivers.Number of days between baseline interview and institutionalization was recorded over an 18-month period. Kaplan-Meier survival analysis with the log rank statistic was used to test for ethnic differences in time to institutionalization. Cox regression analyses were conducted to determine whether care-recipient or caregiver characteristics (e.g., care-recipient age and memory and behavior problems; caregiver depression, years of education, income, and views of the caregiving role) significantly interacted with ethnicity to explain time to institutionalization.Latinas delayed institutionalization significantly longer than their Caucasian counterparts; care-recipient characteristics or caregiver demographics did not explain these results, although Latinas who identified greater benefits or more-positive aspects of the caregiving process at baseline were less likely to institutionalize their loved one than those who reported fewer benefits of caregiving. Less-acculturated Latinas were significantly more likely to identify positive aspects of caregiving than more-acculturated Latinas.Latina dementia caregivers delay institutionalization significantly longer than female Caucasian caregivers. In addition, Latino cultural values and positive views of the caregiving role are important factors that may significantly influence their decision to institutionalize loved ones with dementia.

Abstract

While there has been considerable interest in studying ethnically diverse family caregivers, few studies have investigated the influence of dementia caregiving on Latino families. The current study includes participants from two sites of the REACH (Resources for Enhancing Alzheimer's Caregiver Health) project to compare well-being, appraisal, and religiosity by ethnicity, with specific attention to levels of acculturation. Latina (n = 191) and Caucasian female (n = 229) dementia family caregivers from two regions of the United States (Miami, Florida and Northern California) were compared at baseline on demographics, care recipient characteristics, mental and physical health, and psychosocial resources, including appraisal style and religiosity. Latina caregivers reported lower appraisals of stress, greater perceived benefits of caregiving, and greater use of religious coping than Caucasian caregivers. The relationship of these variables to level of acculturation for the Latina caregivers was also explored. Implications of these results for psychosocial interventions with Latino and Caucasian family caregivers are discussed.

Abstract

To ascertain risk factors for the development of overweight in children at 9.5 years of age.This was a prospective study of 150 children from birth to 9.5 years of age, with assessment of multiple hypothesized risk factors drawn from research reports.Five independent risk factors for childhood overweight were found. The strongest was parent overweight, which was mediated by child temperament. The remaining risk factors were low parent concerns about their child's thinness, persistent child tantrums over food, and less sleep time in childhood. Possible mechanisms by which each of these factors influence weight gain are outlined. Two different pathways to childhood overweight/obesity were found, depending on degree of parental overweight.There is evidence of considerable interaction between parent and child characteristics in the development of overweight. Several of the identified risk factors are amenable to intervention possibly leading to the development of early prevention programs.

Abstract

This study examined health services use in community samples of 102 white and 60 black women with binge eating disorder (BED), 164 white and 85 black healthy comparison women, and 86 white and 21 black women with a noneating Axis I psychiatric disorder.Participants were matched on age, ethnicity, and education and were asked about their use of emergency room visits, outpatient physician visits for medical care, outpatient psychotherapy visits, and days spent in the hospital over the previous 12 months. Total health services use was computed.There were no between-group differences in outpatient physician visits or inpatient hospital days. Relative to healthy comparison women, women with BED and women with other Axis I disorders had increased total health services use, psychotherapy visits, and emergency department visits. Relative to women with noneating Axis I disorders, women with BED had less use of psychotherapy visits. Although obese white women were more likely to report emergency department visits than obese black women were, nonobese white women were less likely to report emergency department visits than nonobese black women were.That health services use by women with BED compared more with that of women with other Axis I disorders than with that of healthy women suggested that BED has clinical significance and is not benign in terms of its impact on the health care system. It appeared, however, that despite the availability of effective treatments, few women with BED received psychotherapy.

Abstract

This study examines a relapse prevention strategy for bulimia nervosa (BN). Subjects in a multicenter BN treatment trial who initially achieved abstinence after a course of cognitive-behavioral therapy (CBT) were told to recontact the clinic if they had a recurrence of symptoms or feared such a reoccurrence so that they could receive additional therapy visits.At the end of CBT, subjects whose scores on the Eating Disorders Examination indicated that they were abstinent from binge eating and purging, and therefore considered to be treated successfully, were assigned randomly to follow-up only or to a crisis intervention model. With the crisis intervention model, subjects would receive additional visits if needed.None of the 30 subjects who relapsed during the follow-up sought additional treatment visits.Simply telling patients with BN who appear to have been successfully treated to come back if they have additional problems, or fear that they are developing such problems, may be an ineffective relapse prevention technique. Alternative strategies, such as planned return visits or phone calls, should be considered as alternative relapse prevention strategies.

Abstract

Disturbed sleep is a major clinical problem in Alzheimer's disease (AD). Apolipoprotein epsilon4 (APOE epsilon4) carrier status may increase risk of AD, yet there are no data on relations between APOE status and progression of sleep disturbance in AD. The objective of this study was to determine if sleep parameters in AD patients change over time as a function of APOE carrier status. Forty-four community-dwelling AD patients with diagnosis of probable AD were followed from early stages of disease. Their sleep/wake parameters were compared according to APOE status. For APOE epsilon4 carriers, only wake after sleep onset (WASO) increased in association with lower cognitive function as indicated by the Mini-Mental State Examination (MMSE); for non-epsilon4 subjects, increases in WASO and declines in total sleep time, sleep efficiency, and the amplitude of the rest/activity circadian rhythm over time were associated with lower performance on the MMSE. In these data, APOE status was associated with the progression of sleep/wake disturbances in AD. Overall, there was greater deterioration on sleep parameters in patients negative for the epsilon4 allele.

Abstract

The purpose of this study was to assess whether pharmacy database information from US Department of Veterans Affairs (VA) medical centers could be used to screen for areas of higher Parkinson's disease prevalence in patients exposed to pesticides. The authors used pharmacy data sets and compared the use of antiparkinsonian medications at 2 VA medical centers in California: one in Palo Alto, near the ocean, and one in Fresno, downwind from extensively farmed parts of the Central Valley. They found that patients at Fresno had higher odds ratios (1.5-1.8) for the use of Parkinson's disease medications than patients at Palo Alto. These data are consistent with the observations of prior epidemiologic studies and suggest that VA pharmacy databases can prioritize locations for further epidemiologic research. However, a thorough exploration of alternative explanations is needed to reach definitive conclusions regarding the findings suggested by this method.

Abstract

We examined 9-month data from the 14-month NIMH Multimodal Treatment Study of Children with ADHD (the MTA) as a further check on the relative effect of medication (MedMgt) and behavioral treatment (Beh) for attention-deficit/hyperactivity disorder (ADHD) while Beh was still being delivered at greater intensity than at 14-month endpoint, and conversely as a check on the efficacy of the MTA behavioral generalization/maintenance procedures. Intention-to-treat analysis at 9 months showed essentially the same results as at 14 months, after Beh had been completely faded; MedMgt and the combination (Comb) of medication and Beh were significantly superior to Beh and community care (CC) for ADHD and oppositional-defiant (ODD) symptoms, with mixed results for social skills and internalizing symptoms. All treatment-group differences examined as changes in slopes from 9 to 14 months were nonsignificant (we found general improvement for all groups). Slopes from baseline to 9 months correlated highly (r > .74, p < .0001) with slopes from baseline to 14 months for all groups. The time function from baseline to 14 months showed a significant linear, but not quadratic, trend for the main outcome measure (a composite of parent- and teacher-rated ADHD and ODD symptoms) for all groups. Findings suggest that in contrast to the hypothesized deterioration in the relative benefit of Beh between 9 and 14 months (after completion of fading), the MTA Beh generalization and maintenance procedures implemented through 9 months apparently yielded continuing improvement through 14 months, with preservation of the relative position of Beh compared to other treatment strategies.

Reconsidering the odds ratio as a measure of 2 x 2 association in a populationSTATISTICS IN MEDICINEKraemer, H. C.2004; 23 (2): 257-270

Abstract

The odds ratio (OR) is probably the most widely used measure of 2x2 association in epidemiology, but it often produces results that are puzzling or misleading. Receiver operating characteristic (ROC) methods are used to take a fresh look at the OR and show where and why such puzzling results arise. When researchers choose to report a summary measure of association, the OR is one of many measures of association that might be considered, not one that should be considered the 'gold standard' of 2x2 measures of association. In a randomized clinical trial with binary outcome for success, either the success or failure rates in treatment and control groups might be reported separately or the number needed to treat to achieve one extra success, to emphasize the cost of unnecessary treatment needed to achieve a success. In studies assessing reliability or heritability, we recommend the intraclass kappa. In studies in which one binary variable is assessed against a binary criterion, we recommend the weighted kappa.

Abstract

Regression analyses are perhaps the most widely used statistical tools in medical research. Centring in regression analyses seldom appears to be covered in training and is not commonly reported in research papers. Centring is the process of selecting a reference value for each predictor and coding the data based on that reference value so that each regression coefficient that is estimated and tested is relevant to the research question. Using non-centred data in regression analysis, which refers to the common practice of entering predictors in their original score format, often leads to inconsistent and misleading results. There is very little cost to unnecessary centring, but the costs of not centring when it is necessary can be major. Thus, it would be better always to centre in regression analyses. We propose a simple default centring strategy: (1) code all binary independent variables +1/2; (2) code all ordinal independent variables as deviations from their median; (3) code all 'dummy variables' for categorical independent variables having m possible responses as 1 - 1/m and -1/m instead of 1 and 0; (4) compute interaction terms from centred predictors. Using this default strategy when there is no compelling evidence to centre protects against most errors in statistical inference and its routine use sensitizes users to centring issues.

Abstract

The arguments pitting categorical versus dimensional approaches to psychiatric diagnosis have been long ongoing with little sign of imminent resolution. We argue that categorical and dimensional approaches are fundamentally equivalent, but that one or other approach is more appropriate depending on the clinical circumstances and research questions being addressed. This paper aims to demonstrate (a) how these two approaches necessarily interdigitate, (b) to clarify the conditions under which one should utilize one approach over the other, and (c) to alert psychiatric clinicians and researchers to issues in the methodology literature that might facilitate their considerations. Using an example from the Infant Health and Development Program (IHDP), we illustrate the importance of using dimensional approaches for hypothesis testing, identify the problems with power and with interpretation that arise from employing a categorical approach, and underscore the importance of identifying the appropriate cutpoints when a categorical approach is necessitated. We argue that failure to utilize the correct approach under the appropriate circumstances can result in impaired clinical and research decision-making.

Abstract

The aims of the present review are to apply a recent risk factor approach (H. C. Kraemer et al., 1997) to putative risk factors for eating disorders, to order these along a timeline, and to deduce general taxonomic questions. Putative risk factors were classified according to risk factor type, outcome (anorexia nervosa, bulimia nervosa, binge-eating disorder, full vs. partial syndromes), and additional factor characteristics (specificity, potency, need for replication). Few of the putative risk factors were reported to precede the onset of the disorder. Many factors were general risk factors; only few differentiated between the 3 eating disorder syndromes. Common risk factors from longitudinal and cross-sectional studies were gender, ethnicity, early childhood eating and gastrointestinal problems, elevated weight and shape concerns, negative self-evaluation, sexual abuse and other adverse experiences, and general psychiatric morbidity. Suggestions are made for the conceptualization of future risk factor studies.

Abstract

We used a novel application of a signal detection technique, receiver operator characteristics (ROC), to describe factors entering a physician's decision to switch a patient from a typical high potency neuroleptic to a particular atypical, olanzapine (OLA) or risperidone (RIS).ROC analyses were performed on pharmacy records of 476 VA patients who had been treated on a high potency neuroleptic then changed to either OLA or RIS.Overall 68% patients switched to OLA and 32% to RIS. The best predictor of neuroleptic choice was age at switch, with 78% of patients aged less than 55 years receiving OLA and 51% of those aged greater than or equal to 55 years receiving OLA (chi(2)=38.2, P<0.001). Further analysis of the former group indicated that adding the predictor of one or more inpatient days to age increased the likelihood of an OLA switch from 78% to 85% (chi(2)=7.3, P<0.01) while further analysis of the latter group indicated that adding the predictor of less than 10 inpatients days to age decreased the likelihood of an OLA switch from 51% to 45% (chi(2)=7.0, P<0.01).ROC analyses have the advantage over other analyses, such as regression techniques, insofar as their "cut-points" are readily interpretable, their sequential use forms an intuitive "decision tree" and allows the potential identification of clinically relevant "subgroups". The software used in this analysis is in the public domain (http://mirecc.stanford.edu).

Abstract

When there exists no single source of information (informant) to validly measure a characteristic, it is typically recommended that data from multiple informants be used. In psychiatric assessment and research, however, multiple informants often provide discordant data, which further confuse the measurement. Strategies such as arbitrarily choosing one informant or using the data from all informants separately generate further problems. This report proposes a theory to explain observed patterns of interinformant discordance and suggests a new approach to using data from multiple informants to measure characteristics of interest.Using the example of assessment of developmental psychopathology in children, the authors propose a model in which the choice of informants is based on conceptualizing the contexts and perspectives that influence expression of the characteristic of interest and then identifying informants who represent those contexts and perspectives in such a way as to have the weaknesses of one informant canceled by the strengths of another.Applications of this approach to several datasets indicate that when these principles are followed, a more reliable and valid consensus measure is obtained, and failure to obtain a reliable, valid measure is indicative of some deviation from the principles.In obtaining a consensus measure, the issue is not determining how many informants are needed but choosing the right set of informants.

Abstract

From the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder--a randomized clinical trial of 579 children ages 7-9 years receiving 14 months of medication management, behavioral treatment, combination, or community care--the authors matched each African American and Latino participant with randomly selected Caucasian participants of same sex, treatment group, and site. Although Caucasian children were significantly less symptomatic than African American and Latino children on some ratings, response to treatment did not differ significantly by ethnicity after controlling for public assistance. Ethnic minority families cooperated with and benefited significantly from combination (multimodal) treatment (d = 0.36, compared with medication). This incremental gain withstood statistical control for mother's education, single-parent status, and public assistance. Treatment for lower socioeconomic status minority children, especially if comorbid, should combine medication and behavioral treatment.

Abstract

The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine)=0.80; ES (donepezil)=1.02; ES (alcohol acute)=-3.66; ES (alcohol 8 h)=-0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

Abstract

Epidemiological studies of eating disorders in the United States have focused on white women and girls, and the prevalence of eating disorders in ethnic minority groups is unknown. This study examined the prevalence of anorexia nervosa, bulimia nervosa, and binge eating disorder in a geographically and economically diverse community sample of young white and black women who previously participated in the 10-year National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study.All NHLBI Growth and Health Study participants were recruited for this study. A two-stage case finding method was used, consisting of a telephone screening (sensitivity=0.90, specificity=0.98) and an in-person confirmatory diagnostic interview.A total of 86.0% of the original NHLBI Growth and Health Study cohort participated, including 985 white women (mean age=21.3) and 1,061 black women (mean age=21.5). Fifteen white (1.5%) and no black women met lifetime criteria for anorexia nervosa; more white women (N=23, 2.3%) than black women (N=4, 0.4%) met criteria for bulimia nervosa; binge eating disorder also was more common among white women (N=27, 2.7%) than black women (N=15, 1.4%). Few women (white: N=16, 28.1%; black: N=1, 5.3%) ever had received treatment for an eating disorder.Results suggest that eating disorders, especially anorexia nervosa and bulimia nervosa, are more common among white women than among black women. The low treatment rates in both groups suggest that health professionals need to be more alert to the possibility of eating disorders in women.

Abstract

This study was initiated by breast cancer survivors living in a rural community in California. They formed a partnership with academic researchers to develop and evaluate a low-cost, community-based Workbook-Journal (WBJ) for improving psychosocial functioning in geographically and economically isolated women with primary breast cancer.A randomized controlled trial was used to compare the WBJ intervention plus educational materials to educational materials alone (usual care).One rural cancer center and several private medical, surgical, and radiation oncology practices in 7 rural counties in the Sierra Nevada Foothills of California.One hundred women with primary breast cancer who were either within 3 months of diagnosis or within 3 months of completing treatment.A community-initiated, theoretically-based Workbook-Journal, designed by rural breast cancer survivors and providers as a support group alternative. It included compelling personal stories, local rural resources, coping strategies, and messages of hope.Community recruiters enrolled 83% of the women referred to the study. Retention at 3-month follow-up was 98%. There were no main effects for the WBJ. However, 3 significant interactions suggested that women who were treated in rural practices reported decreased fighting spirit and increased emotional venting and posttraumatic stress disorder symptoms if they did not receive the WBJ. Among women who receive the WBJ, 74% felt emotionally supported.This community-based Workbook-Journal may be an effective psychosocial intervention for rural, isolated, and low-income women with breast cancer. Community involvement was essential to the success of this project.

Abstract

To investigate effects of the timing of initial exposure to maternal depression and marital conflict on kindergarten children's mental health symptoms.For 406 families (of 570 originally recruited), mothers reported on major depression and marital conflict on multiple occasions in the child's infancy and toddler/preschool periods. Mothers and teachers completed the MacArthur Health and Behavior Questionnaire when children were in kindergarten.Children evidenced co-occurring internalizing and externalizing symptoms, although the mix was more toward internalizing for girls and externalizing for boys. Symptoms were more severe among children exposed to either adversity, and these effects were additive. Boys exposed to maternal depression in infancy had a preponderance of internalizing behaviors, but if subsequently exposed to marital conflict, the mix toward externalizing behaviors increased to match levels of clinic-referred children. For girls, the preponderance of internalizing symptoms increased to match levels of clinic-referred children when initial exposure to marital conflict occurred in the toddler/preschool period.It is important to consider both adversities across developmental periods, to distinguish the symptom severity from directionality, and to consider child gender. Prevention and intervention efforts that consider these findings are warranted.

Abstract

Using receiver operating characteristics, the authors examined outcome predictors (variables associated with outcome regardless of treatment) and moderators (variables identifying subgroups with differential treatment effectiveness) in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD; MTA). Treatment response was determined using parent- and teacher-reported ADHD and oppositional defiant symptoms, with levels near or within the normal range indicating excellent response. Among 9 baseline child and family characteristics, none predicted but 3 moderated treatment response. In medication management and combined treatments, parental depressive symptoms and severity of child ADHD were associated with decreased rates of excellent response; when these 2 characteristics were present, below-average child IQ was an additional moderator. No predictors or moderators emerged for behavioral and community comparison treatments. The authors discuss conceptual and clinical implications of research on treatment moderators.

Abstract

The aim of this study was to validate a computer-assisted screening battery for classifying patients into two groups, those with and without cognitive impairment. Participants were all patients referred to the neuropsychology clinics at four VA medical centers during a 1-year period. Patients meeting the study inclusionary criteria (N = 252) were administered the Neurobehavioral Evaluation System-3 (NES3) computer-assisted battery. A detailed neuropsychological examination was carried out by an experienced neuropsychologist, who diagnosed the patient as cognitively impaired or not impaired. The neuropsychologist's diagnosis was the gold standard. Recursive partitioning analyses yielded several classification procedures using the NES3 data to predict the gold standard These procedures produced a set of six NES3 tasks that provide good sensitivity and specificity in predicting di- agnosis. Sensitivity and specificity for the least random classification procedure were 0.87 and 0.67, respectively. The results suggest that computer-assisted screening methods are a promising means of triaging patients.

Abstract

This study examined the importance of potential risk factors for eating disorder onset in a large multiethnic sample followed for up to 3 years, with assessment instruments validated for the target population and a structured clinical interview used to make diagnoses.Participants were 1,103 girls initially assessed in grades 6-9 in school districts in Arizona and California. Each year, students completed the McKnight Risk Factor Survey, had body height and weight measured, and underwent a structured clinical interview. The McKnight Risk Factor Survey, a self-report instrument developed for this age group, includes questions related to risk factors for eating disorders.During follow-up, 32 girls (2.9%) developed a partial- or full-syndrome eating disorder. At the Arizona site, there was a significant interaction between Hispanics and higher scores on a factor measuring thin body preoccupation and social pressure in predicting onset of eating disorders. An increase in negative life events also predicted onset of eating disorders in this sample. At the California site, only thin body preoccupation and social pressure predicted onset of eating disorders. A four-item screen derived from thin body preoccupation and social pressure had a sensitivity of 0.72, a specificity of 0.80, and an efficiency of 0.79.Thin body preoccupation and social pressure are important risk factors for the development of eating disorders in adolescents. Some Hispanic groups are at risk of developing eating disorders. Efforts to reduce peer, cultural, and other sources of thin body preoccupation may be necessary to prevent eating disorders.

Abstract

A brief review of the "rules" of evidence in assessing the efficacy and effectiveness of treatments leads to a discussion of what the future might hold in the development of the rules of randomized clinical trials (RCTs) in order to enhance the impact of such studies. The primary requisite for enhancing the impact of studies appears to be discussions and interactions among researchers, clinicians, policy makers, and patient advocates, on the one hand, and among the basic scientists and clinical researchers, on the other.

Abstract

Little information exists on relapse in patients with bulimia nervosa who responded with complete abstinence from binge eating and purging to cognitive behavioral therapy. Identification of relapse predictors may be useful to design effective early intervention strategies for relapse of susceptible patients with bulimia nervosa.This multisite study examined relapse in 48 patients with bulimia nervosa who had responded to cognitive behavioral therapy with complete abstinence from binge eating and purging. Structured interviews and questionnaires were used to assess patients before and after treatment and at 4 months after treatment.Four months after treatment, 44% of the patients had relapsed. Those who relapsed had a higher level of preoccupation and ritualization of eating and less motivation for change, and had maintained abstinence for a shorter time during the treatment period.The predictors of relapse found in this study can be readily determined by clinicians. The effectiveness of early additional treatment interventions needs to be determined with well-designed studies of large samples.

Abstract

Particularly in psychiatry, biological measures are increasingly sought to detect exposure to toxic agents, to assist in early identification of illness, and to enhance diagnostic certainty, provide prognostic information, and permit the mapping of outcome in a variety of disorders. The authors explore the fundamental criteria necessary to designate a biological measure as a "biomarker" and discuss the potential applications, limitations, and hazards of such markers. Authors discuss methods for establishing the validity of a biomarker. Finally, they convey a word of caution about overinterpreting the clinical or scientific value of any biological measure.

Abstract

The diagnostic criteria for anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) establish symptom severity levels, which are used to separate full cases from partial cases. However, the value of these distinctions is unclear.Three hundred eighty-five women with full or partial AN, BN, or BED were assessed at entry into a longitudinal study of eating disorders.Stepwise discriminant analysis revealed that full and partial BN were discriminated by the Yale-Brown-Cornell Eating Disorders Scale total scores (kappa =.46). However, it was not possible to discriminate between full and partial AN or BED. Discriminant analysis also demonstrated clear differences between full AN, BN, and BED.Full BN can be differentiated from partial BN by more severe eating disorder symptoms, whereas both full and partial AN and full and partial BED appear quite similar. These results emphasize the distinct nature of AN, BN, and BED, as well as the similarities between full and partial cases.

Abstract

Since the description of bulimia nervosa as a distinct diagnostic entity in 1979, several psychological and pharmacological interventions have been developed and empirically tested. The existence of several effective treatments, none of which is completely effective, is common to most psychiatric conditions. The research question that flows from such findings is whether second-level treatments would be effective for those who fail initial treatment.In the case of bulimia nervosa, the research findings suggest that cognitive behavioral therapy (CBT) is the first level of treatment and that both antidepressant medication and interpersonal psychotherapy (IPT) may potentially be effective second-level treatments. This was a multicenter study in which 194 patients were initially treated with CBT. Those treated unsuccessfully (n = 62) were then randomized to treatment with IPT or medication management.Of those assigned to secondary treatment, 37 completed such treatment and 25 dropped out or were withdrawn. The abstinence rate for subjects assigned to treatment with IPT was 16% and for those assigned to medication management was 10%. No significant differences were found between medication and IPT in either the intent-to-treat or completer analysis.Dropout rates were high, and response rates were low among BN patients assigned to secondary treatments who failed to achieve remission with CBT. Offering lengthy sequential treatments appears to have little value, and alternative models for therapy need to be tested.

Abstract

Randomized clinical trials (RCTs) not only are the gold standard for evaluating the efficacy and effectiveness of psychiatric treatments but also can be valuable in revealing moderators and mediators of therapeutic change. Conceptually, moderators identify on whom and under what circumstances treatments have different effects. Mediators identify why and how treatments have effects. We describe an analytic framework to identify and distinguish between moderators and mediators in RCTs when outcomes are measured dimensionally. Rapid progress in identifying the most effective treatments and understanding on whom treatments work and do not work and why treatments work or do not work depends on efforts to identify moderators and mediators of treatment outcome. We recommend that RCTs routinely include and report such analyses.

Abstract

Part of the challenge in research on degenerative neurologic disease relates to distinguishing those measurements that essentially describe patient characteristics stable across the course of illness (traits) from those that vary systematically within subjects (states), particularly those specifically related to stage or duration of illness. A components-of-variance approach was used to examine the state versus trait aspects of the Alzheimer's Disease Assessment Scale (ADAS) Cognitive and Noncognitive subscales, a clinical instrument frequently used in research on Alzheimer disease. Subjects were 190 patients with probable AD followed longitudinally. Stage of illness was indexed by mental status scores. Analysis of variance was used to partition total variance into that associated with subjects (trait), stages (state: stage), subjects x stages (state: other), and error. ADAS Cognitive scores were strongly related to stage of illness (83% of true variance). ADAS Noncognitive scores were modestly related to stage (approximately 21% of true variance) and moderately related to state: other (47%). We discuss how state-trait analyses can be helpful in focusing attention on those areas of assessment most likely to accomplish specific objectives.

Abstract

A major factor in the context of evaluating depression in the elderly is the role of medical problems. With aging there is a rapid increase in the prevalence of a number of medical disorders, including cancer, heart disease, Parkinson's disease, Alzheimer's disease, stroke, and arthritis. In this article, we hope to bring clarity to the definition of comorbidity and then discuss a number of medical disorders as they relate to depression. We evaluate medical comorbidity as a risk factor for depression as well as the converse, that is, depression as a risk factor for medical illness. Most of the disorders that we focus on occur in the elderly, with the exception of HIV infection. This review focuses exclusively on unipolar disorder. The review summarizes the current state of the art and also makes recommendations for future directions.

Abstract

A number of systems have been proposed for classifying older adults who suffer from cognitive impairment or decline but do not yet meet criteria for Alzheimer's disease (AD). The classification, Mild Cognitive Impairment (MCI), has attracted much attention. It uses relatively specific diagnostic criteria and individuals who meet these criteria appear to be at substantial risk for the development of AD. However, little data is available to define the prevalence of MCI in any age group. We propose a simple mathematical model for the progression of patients from Non-Affected (NA) to MCI to AD. This first-order Markov model defines the likely prevalence of MCI at specific ages. Primary assumptions of the model include an AD prevalence of 1% at age 60 increasing to 25% at age 85 and a conversion rate from MCI to AD of 10% constant across all ages considered. We used the best available information for our model and found (1) that the MCI prevalence increased from 1% at age 60 to 42% at age 85 and (2) that the conversion rate from NA to MCI increased from 1% per year at age 60 to 11% at age 85. In conclusion, this model allows estimation of prevalence of MCI and conversion from NA to MCI based upon known prevalences of AD, conversion rates of MCI to AD, and death rates. Due to its substantial prevalence, MCI may be an important target for screening and possible intervention.

Abstract

Four relatively independent emotion-regulation constructs (suppression of negative affect, restraint, repression, and emotional self-efficacy) were tested as outcomes in a randomized trial of supportive-expressive group therapy for women with metastatic breast cancer. Results indicate that report of suppression of negative affect decreased and restraint of aggressive, inconsiderate, impulsive, and irresponsible behavior increased in the treatment group as compared with controls over 1 year in the group. Groups did not differ over time on repression or emotional self-efficacy. This study provides evidence that emotion-focused therapy can help women with advanced breast cancer to become more expressive without becoming more hostile. Even though these aspects of emotion-regulation appear trait-like within the control group, significant change was observed with treatment.

Abstract

Examined hypothesized gender and comorbidity differences in the observed classroom behavior of children with attention deficit hyperactivity disorder (ADHD). The behavior of 403 boys and 99 girls with ADHD, ages 7-10, was compared (a) to observed, sex-specific classroom behavior norms, (b) by sex, and (c) by comorbid subgroups. Boys and girls with ADHD deviated significantly from classroom norms on 15/16 and 13/16 categories, respectively. Compared to comparison girls, girls with ADHD had relatively high rates of verbal aggression to children. Boys with ADHD engaged in more rule-breaking and externalizing behaviors than did girls with ADHD, but the sexes did not differ on more "neutral," unobtrusive behaviors. The sex differences are consistent with notions of why girls with ADHD are identified and referred later than boys. Contrary to hypothesis, the presence of comorbid anxiety disorder (ANX) was not associated with behavioral suppression; yet, as hypothesized, children with a comorbid disruptive behavior disorder (DBD) had higher rates of rule-breaking, and impulsive and aggressive behavior, than did children with ADHD alone and those with ADHD+ANX. Elevated rates of ADHD behaviors were also observed in children with comorbid DBD, indicating that these behaviors are truly present and suggesting that reports of higher ADHD ratings in this subgroup are not simply a consequence of negative halo effects and rater biases.

Abstract

In the December 2000 issue of the Journal of Abnormal Child Psychology, we published a set of papers presenting secondary analyses of the Multimodal Treatment Study of ADHD (MTA), and R. A. Barkley (2000) provided a commentary. A critique of the design of the study (MTA Cooperative Group, 1999) was presented based on a theoretical perspective of a "behavioral inhibition" deficit that has been hypothesized as the core deficit of ADHD (R. A. Barkley, 1997). The commentary questioned the design and analysis of the MTA in terms of (1) the empirical criteria for selection of components of behavioral (Beh) intervention, (2) the effectiveness of the Beh intervention, (3) the methods for analyses at the group and individual level, (4) implications of the MTA findings for clinical practice, (5) the role of genetics in response to treatment, and (6) the lack of a nontreatment control group. In this response, we relate the content of the papers to the commentary, (1) by reviewing the selection criteria for the Beh treatment, as outlined by K. C. Wells, W. E. Pelham, et al. (2000), (2) by addressing the myth that the MTA Beh treatment was ineffective (Pelham, 1999), (3) by describing the use of analyses at the level of the individual participant, as presented by J. S. March et al. (2000) and W. E. Pelham et al. (2000) as well as elsewhere by J. M. Swanson et al. (2001) and C. K. Conners et al. (2001), (4) by relating some of the suggestions from the secondary analyses about clinically relevant factors such as comorbidity (as presented by J. S. March et al., 2000) and family and parental characteristics (as presented by B. Hoza et al., 2000, S. P. Hinshaw et al., 2000, and K. C. Wells, J. N. Epstein, et al., 2000), (5) by discussing the statistical concept of heritability and the lack of a significant difference in the presence of ADHD symptoms in parents of the MTA families compared to parents in the classmate-control families (as presented by J. N. Epstein, et al., 2000), and (6) by acknowledging that an ethically necessary weakness of the MTA design is that it did not include a no-treatment control group. We discuss the use of secondary analyses to suggest how, when, and for what subgroups effectiveness of the Beh treatment may have been manifested. Finally, we invite others to use the large and rich data set that will soon be available in the public domain, to perform secondary analyses to mine the meaning of the MTA and to evaluate theories of ADHD and response to treatments.

Abstract

Using data from 4 smoking cessation trials conducted from 1988 to 2000, the authors investigated whether men are more successful than women in quitting smoking. Odds ratios indicated that the abstinence rates were not significantly different for men and women. Thus, there may be little value to diverting research funds from efforts to develop more effective treatments for both men and women to efforts to explain a very small gender effect associated with existing treatments. However, it may be appropriate to make gender comparisons for new therapies for nicotine dependence. The authors recommend against analyses of gender differences in studies that do not account for gender in their research designs.

Abstract

We examined the interactive influence of specific demographic and diagnostic variables on Benton Visual Retention Test (BVRT) performance in three commonly presenting groups of older adults. Cross-sectional data from three archival samples were utilized: "normals" (n=156), "normals with memory concerns" (n=435), and a "mixed neurologic" group (n=196). In both normal groups, as well as in a "no/low deficit" neurologic subgroup, we confirmed that the higher one's age, the lower their BVRT accuracy, while the higher one's level of education, the greater their BVRT accuracy (at least through age 84). For normal subjects, gender had no impact on BVRT performance. Variability in BVRT performance increased consistently, but not significantly, through age 85.

Abstract

Kappa coefficients are measures of correlation between categorical variables often used as reliability or validity coefficients. We recapitulate development and definitions of the K (categories) by M (ratings) kappas (K x M), discuss what they are well- or ill-designed to do, and summarize where kappas now stand with regard to their application in medical research. The 2 x M(M>/=2) intraclass kappa seems the ideal measure of binary reliability; a 2 x 2 weighted kappa is an excellent choice, though not a unique one, as a validity measure. For both the intraclass and weighted kappas, we address continuing problems with kappas. There are serious problems with using the K x M intraclass (K>2) or the various K x M weighted kappas for K>2 or M>2 in any context, either because they convey incomplete and possibly misleading information, or because other approaches are preferable to their use. We illustrate the use of the recommended kappas with applications in medical research.

Abstract

We explored the possibility that the administration of intravenous dopamine increases the risk for delirium as manifested by need for haloperidol.This study was based on a retrospective analysis. To examine the contribution of dopamine in the prediction of need for haloperidol, a multivariate logistic regression model was used.University hospital.All inpatient admissions to Stanford University Hospital over a 1-year period (n = 21,844).None.Dopamine administration was associated with nearly a tripling of the odds of subsequent need of the antipsychotic drug (chi-square = 108, df = 1, p =.0001, odds ratio = 2.89), even after intensive care unit admission and diagnostic related group weight were considered as indicators of severity of illness. Even when analysis was limited to patients seen in the intensive care unit setting (n = 3,308), dopamine administration remained a very strong risk factor for haloperidol and hence possibly for delirium. The increased risk of need for haloperidol in patients administered dopamine is evident in every age group after age 20.The retrospective nature of this study, the inexact method to assess acuity, and, most of all, the use of haloperidol as an indicator of the presence of delirium preclude concluding that dopamine is directly a risk factor for delirium, much less a causal risk factor. However, the association is potent enough to suggest this possibility strongly and thus supports the need for prospective studies to examine the relationship between dopamine and delirium and to consider possible prophylactic treatment against delirium in those given dopamine.

Abstract

The present study examined the longitudinal relationship between depressive symptoms and coping strategies in older adult primary caregivers of noninstitutionalized Alzheimer's patients. Coping and depression were measured in 51 healthy, nondepressed caregivers (37 women, 14 men) at 4 times of testing approximately 6 months apart. The caregivers' coping strategies and depressive symptoms were found to be largely stable over all times of testing-with a recently developed method for evaluating construct stability-despite significant decline in the patients' cognitive functioning over the same interval. Avoidance coping was also found to be positively associated with depressive symptoms. Results suggest that a strong stable component is present in caregiver coping style and that caregiver intervention researchers may want to examine the extent to which commonly used outcome measures are assessing stable caregiver traits rather than state-dependent distress.

Abstract

(1) To evaluate the psychometric properties of the MacArthur Health and Behavior Questionnaire (HBQ) in two studies of 4- to 8-year-old children and (2) to explore the empirical and theoretical implications of HBQ-based study findings.Samples of children were recruited from (1) mental health clinics (n = 53) and community schools (n = 67) for a case-control study in three research sites and (2) a Wisconsin-based community cohort study of families and work, comprising children with high levels of internalizing and/or externalizing behavior problems and asymptomatic children (N = 122). Combinations of mothers, fathers, and teachers completed the HBQ at one or two time points in four geographically and culturally distinctive settings.Assessment of HBQ reliability showed high test-retest stability and cross-informant agreement. The instrument discriminated strongly and significantly among symptom groups (i.e., high internalizing, high externalizing, high both, and low both) and showed moderate to large effect sizes for between-group differences. Substantial covariance was also found among the HBQ mental, physical, social, and academic problem subscales.The HBQ is a reliable and valid parent- and teacher-report instrument for assessing multiple dimensions of health and dysfunction in middle childhood and for identifying children on whom more intensive diagnostic procedures may be warranted. Confluences among the four health dimensions suggest phenomenological and perhaps etiological commonalities among traditionally partitioned childhood difficulties and suggest possible artificiality in the conventional distinction between pediatric and child psychiatric morbidities.

Abstract

Treatment studies in child and adolescent psychiatry are increasingly characterized by long-term, multisite, randomized clinical trials (RCTs). During the course of these RCTs it is common for clinical exigencies to emerge that require rapid, direct intervention. The challenge is to provide clinically appropriate responses that do not contaminate the delivery, distinctness, and interpretation of the treatments under investigation. In multisite studies, the problem is compounded by the need to minimize cross-site differences in the delivery of adjunct treatments. Such minimization requires fully operationalized and manual-based procedures for clinically mandated intervention. The NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (ADHD)--"the MTA"--is a long-term multisite collaborative study in which children with ADHD were randomly assigned to either medication management, behavioral treatment, the combination, or community-comparison assessment and referral. In designing its study, the MTA developed a manual-based set of procedures (the MTA Adjunct Services and Attrition Prevention [ASAP] Manual) for situations not covered by the protocol treatments. The majority of cases requiring adjunct services fell into two major categories: (1) crisis/emergent situations and (2) imminent risk of attrition. This report describes the ASAP guidelines for dealing with cases that required adjunct services that the MTA Steering Committee adopted before initiating the trial. Although the manual-based guidelines are especially applicable to multisite RCTs, many of the procedures in the ASAP Manual can apply to any treatment study in children.

Abstract

Three sites collaborated to evaluate the differential performance of the MacArthur Health and Behavior Questionnaire (HBQ) and the Diagnostic Interview Schedule for Children Version IV (DISC-IV) in identifying DSM-IV psychopathology in young children.A sample of 120 four- to eight-year-old nonreferred (community) (n = 67) and referred (clinical) (n = 53) children was examined. Mothers reported on their child's mental health symptoms using the HBQ (a dimensional measure with a clinical cutoff score) and the DISC-IV. Teachers independently reported on the child's symptoms and impairment in school using the teacher HBQ. Children self-reported on their symptoms using the companion Berkeley Puppet Interview.On the basis of its derived clinical cutoff scores, the HBQ identified significantly more children with clinical symptoms of DSM-IVinternalizing psychopathology than the DISC-IV in both referred and nonreferred groups. There was a high level of agreement between the two measures in the identification of externalizing psychopathology. Children identified as having internalizing psychopathology by the HBQ were also rated as highly symptomatic and impaired by teachers.The findings support the general validity of the parent HBQ for the assessment of young child psychopathology and the hypothesis that it captures more internalizing psychopathology than the DISC-IV in this population.

Abstract

Cognitive-behavioral therapy (CBT) is an effective treatment of bulimia nervosa, but its mechanisms of action have not been established. In this study the authors analyzed the results of a randomized control trial comparing CBT with Interpersonal Psychotherapy (IPT) to identify possible mediators of change of CBT for BN and its time course of action. Reduction in dietary restraint as early as Week 4 mediated posttreatment improvement in both binge eating and vomiting. Measures of self-efficacy concerning eating behavior, negative affect, and body shape and weight at midtreatment were also significantly associated with posttreatment outcome at 20 weeks. No evidence was found that the therapeutic alliance mediated treatment outcome. CBT had a significantly more rapid treatment effect than IPT, with 62% of posttreatment improvement evident by Week 6.

Abstract

Major advances in understanding the physiology and genetics of circadian rhythm in the past decade challenge the researcher of sleep/wake disorders in Alzheimer's disease (AD) to distinguish patient characteristics stable across the course of illness ("traits") from characteristics that vary with stage of illness ("states"). A components-of-variance approach with a repeated measures model was used to examine the between-subjects variance over time ("trait") vs. within-subjects ("state") variance in 42 patients with probable AD followed, on average, over 2 years on actigraphic sleep/wake measures. Mental status scores indexed stage of illness. Actigraphic measures of sleep efficiency and circadian rhythmicity appeared predominantly "trait," with between-individual differences accounting for over 55% of variance compared to the less than 5% of variance related to stage of cognitive impairment. We discuss how "state-trait" analyses can be helpful in identifying areas of assessment most likely to be fruitful objectives of physiologic and genetic research on sleep/wake disturbance in AD.

Identification of population subgroups of children and adolescents with high asthma prevalence - Findings from the Third National Health and Nutrition Examination SurveyARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINERodriguez, M. A., Winkleby, M. A., Ahn, D., Sundquist, J., Kraemer, H. C.2002; 156 (3): 269-275

Abstract

To provide national estimates of asthma prevalence in African-American, Mexican American and white (non-Latino) children and adolescents using several common definitions; to evaluate familial, sociodemographic, and environmental risk factors that are independently associated with current asthma in children; and to identify subgroups at particular risk for current asthma using 2 complementary data analytic approaches.Cross-sectional study, using the Third National Health and Nutrition Examination Survey, 1988-1994.Eighty-nine mobile examination centers in the United States.Twelve thousand three hundred eighty-eight African American, Mexican American, and white (non-Latino) children and adolescents, aged 2 months through 16 years, selected from a systematic random, population-based, nationally representative sample.Current asthma, defined by caregivers who reported that their child currently had doctor-diagnosed asthma.The overall prevalence of current asthma was 6.7% (95% confidence interval [CI], 5.6-7.8). Odds ratios for current asthma from the multiple regression analysis were 4.00 (95% CI, 2.90-5.52) for children with a parental history of asthma or hay fever, 1.94 (95% CI, 1.09-3.46) for children with body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than or equal to the 85th percentile, and 1.64 (95% CI, 1.20-2.26) for children of African American ethnicity. African American and Mexican American children showed a consistent prevalence of current asthma across age while white children showed an increase in prevalence with age. The 2 highest-risk subgroups identified by the signal detection analysis were composed of children with a parental history of asthma or hay fever who were 10 years or older with a body mass index greater than or equal to the 85th percentile (31.0% current asthma), and children with a parental history who were 10 years or younger and of African American ethnicity (15.6% current asthma).The findings from this analysis show a strong independent association between obesity and current asthma in children and adolescents, and confirm previous reports of a parental history of asthma or hay fever and African American ethnicity as additional important risk factors.

Abstract

OBJECTIVES: (a) To determine the quantity and quality of behavioral problems in older hospitalized patients on acute care units; (b) to determine the burden of these behaviors on staff; and (c) to identify predictors of behavioral problems. METHODS: Upon admission, patients performed the Mini-Mental State Exam (MMSE), the Geriatric Depression Scale (GDS), and information was obtained on age, ethnicity, level of education, living arrangement, and psychiatric history. Two days post-admission, a clinical staff member caring for each patient, performed the Neuropsychiatric Inventory-Questionnaire (NPI-Q) to assess patients' behavioral problems and staff distress. PARTICIPANTS AND SETTING : Forty-two patients, over 60 years of age, admitted to medical and surgical units of the Veterans Affairs Hospitals in Palo Alto and San Francisco, participated. RESULTS: Twenty-three of 42 (55%) patients exhibited behavioral problems. Anxiety, depression, irritability, and agitation/aggression were the most frequently observed behaviors. The severity of the behavioral problems was significantly correlated with staff distress. Lower performance on the MMSE at admission was significantly associated with higher NPI-Q ratings. Specifically, of those cases with scores less than or equal to 27 on the MMSE, 66% had behavioral problems during hospitalization, compared to only 31% of those with scores greater than 27. CONCLUSION: Behavioral problems in older hospitalized patients appear to occur frequently, are a significant source of distress to staff, and can result in the need for psychiatric consultation. Assessment of the mental status of older adults at admission to hospital may be valuable in identifying individuals at increased risk for behavioral problems during hospitalization.

Abstract

In the current study of 1062 Alzheimer's disease (AD) patients, we employed receiver operating characteristic curve analysis to identify characteristics of patients at increased risk for rapid cognitive decline. The patients are participants at one of the nine Alzheimer's Disease Research Centers of California. Rapid decline was defined as a 3-point or greater loss on the Mini-Mental State Examination (MMSE) per year, post visit. The independent variables were age at clinic visit, age at symptom onset of AD, MMSE at patient visit, years of education, gender, ethnicity, living arrangement, presence of aphasia, delusions, hallucinations, and extrapyramidal signs. Receiver operating characteristic curve analysis indicated that AD patients presenting with moderate to severe aphasia, age at clinic visit of 75 years or less, and an MMSE greater than 7 were at increased risk for rapid cognitive decline. This information could help clinicians target these patients for pharmacologic interventions, facilitate long-term care planning, and potentially create savings by delaying or stabilizing the course of the disease.

Abstract

B. Rind, P. Tromovitch, and R. Bauserman (1998) examined the long-term effects of childhood sexual abuse (CSA) by meta-analyzing studies of college students. The authors reported that effects "were neither pervasive nor typically intense" and that "men reacted much less negatively than women" (p. 22) and recommended value-neutral reconceptualization of the CSA construct. The current analysis revealed numerous problems in that study that minimized CSA-adjustment relations, including use of a healthy sample, an inclusive definition of CSA, failure to correct for statistical attenuation, and misreporting of original data. Rind et al.'s study's main conclusions were not supported by the original data. As such, attempts to use their study to argue that an individual has not been harmed by sexual abuse constitute a serious misapplication of its findings.

Abstract

We examined the effect of the apolipoprotein E (apo E) epsilon4 allele on the relationship between self-reported stress and mood in caregivers of patients with Alzheimer's disease. Eighty-six female subjects between the ages of 28 and 82 years who were community-dwelling AD patient caregivers participated in the study. A cross-sectional analysis of stress and mood was performed using the Revised Memory and Behavior Problem Checklist and the Geriatric Depression Scale. All subjects were evaluated for normal cognitive function (Mini-Mental Status Examination) and apo E genotype. The results indicated that increased levels of stress were associated with increased levels of depressive symptoms in nondemented caregivers with the epsilon4 allele. This relationship was not observed in caregivers without the epsilon4 allele. These results suggest that carriers of the epsilon4 allele may respond differently to psychological stress than do individuals without the epsilon4 allele.

Abstract

We hypothesized that children's perceptions of more neighborhood hazards would be associated with less physical activity, less aerobic fitness, and a higher body mass index.To examine the association between a hazardous neighborhood context and physical activity in children.Fourth-grade students (n = 796) of diverse ethnic and economic backgrounds completed measures of neighborhood hazards, self-reported physical activity, physical fitness, height, and weight. Parents (n = 518) completed telephone interviews and provided data on their education level and occupation.As expected, children from families of lower socioeconomic status perceived significantly more neighborhood hazards. Contrary to our hypothesis, the perception of more hazards was significantly associated with more reported physical activity. This finding was not explained by school heterogeneity, alteration of the hazards measure, or differences in socioeconomic status.To further examine the relationship between neighborhood hazards and physical activity, we suggest that future studies include assessments of sedentary behavior, parental fear of violence, parental regulation of children's leisure activities, and cost and quality of available play areas and organized sports.

Abstract

The authors developed a methodological basis for investigating how risk factors work together. Better methods are needed for understanding the etiology of disorders, such as psychiatric syndromes, that presumably are the result of complex causal chains.Approaches from psychology, epidemiology, clinical trials, and basic sciences were synthesized.The authors define conceptually and operationally five different clinically important ways in which two risk factors may work together to influence an outcome: as proxy, overlapping, and independent risk factors and as mediators and moderators.Classifying putative risk factors into these qualitatively different types can help identify high-risk individuals in need of preventive interventions and can help inform the content of such interventions. These methods may also help bridge the gaps between theory, the basic and clinical sciences, and clinical and policy applications and thus aid the search for early diagnoses and for highly effective preventive and treatment interventions.

Abstract

Previous attempts to reduce the effects of television advertising on children's purchase requests have had little success. Therefore, we tested the effects of a classroom intervention to reduce television, videotape, and video game use on children's toy purchase requests, in a school-based randomized controlled trial. Third- and fourth-grade children (mean age, 8.9 years) in two sociodemographically and scholastically matched public elementary schools were eligible to participate. Children in one randomly selected elementary school received an 18-lesson, 6-month classroom curriculum to reduce television, videotape, and video game use. In both schools, in September (before intervention) and April (after intervention) of a single school year, children and parents reported children's prior week's purchase requests for toys seen on television. After intervention, children in the intervention school were significantly less likely to report toy purchase requests than children in the control school, with adjusting for baseline purchase requests, gender, and age (odds ratio, 0.29; 95% confidence interval, 0.12-0.69). Among intervention school children, reductions in self-reported purchase requests were also associated with reductions in television viewing. There was no significant difference between schools in parent reports of children's requests for toy purchases. These findings suggest that reducing television viewing is a promising approach to reducing the influences of advertising on children's behavior.

Abstract

Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control.Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population.Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition.Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.

Abstract

Identifying subgroups of high-risk individuals can lead to the development of tailored interventions for those subgroups. This study compared two multivariate statistical methods (logistic regression and signal detection) and evaluated their ability to identify subgroups at risk. The methods identified similar risk predictors and had similar predictive accuracy in exploratory and validation samples. However, the 2 methods did not classify individuals into the same subgroups. Within subgroups, logistic regression identified individuals that were homogeneous in outcome but heterogeneous in risk predictors. In contrast, signal detection identified individuals that were homogeneous in both outcome and risk predictors. Because of the ability to identify homogeneous subgroups, signal detection may be more useful than logistic regression for designing distinct tailored interventions for subgroups of high-risk individuals.

Abstract

To develop a categorical outcome measure related to clinical decisions and to perform secondary analyses to supplement the primary analyses of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA).End-of-treatment status was summarized by averaging the parent and teacher ratings of attention-deficit/hyperactivity disorder and oppositional defiant disorder symptoms on the Swanson, Nolan, and Pelham, version IV (SNAP-IV) scale, and low symptom-severity ("Just a Little") on this continuous measure was set as a clinical cutoff to form a categorical outcome measure reflecting successful treatment. Three orthogonal comparisons of the treatment groups (combined treatment [Comb], medication management [MedMgt], behavioral treatment [Beh], and community comparison [CC]) evaluated hypotheses about the MTA medication algorithm ("Comb + MedMgt versus Beh + CC"), multimodality superiority ("Comb versus MedMgt"), and psychosocial substitution ("Beh versus CC").The summary of SNAP-IV ratings across sources and domains increased the precision of measurement by 30%. The secondary analyses of group differences in success rates (Comb = 68%; MedMgt = 56%; Beh = 34%; CC = 25%) confirmed the large effect of the MTA medication algorithm and a smaller effect of multimodality superiority, which was now statistically significant (p < .05). The psychosocial substitution effect remained negligible and nonsignificant.These secondary analyses confirm the primary findings and clarify clinical decisions about the choice between multimodal and unimodal treatment with medication.

Abstract

To conduct a post hoc investigation of the utility of a single composite measure of treatment outcome for the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) at 14 months postbaseline.Examination of multiple measures one at a time in the main MTA intent-to-treat outcome analyses failed to detect a statistically significant advantage of combined treatment (Comb) over medication management (MedMgt). A measure that increases power and precision using a single outcome score may be a useful alternative to multiple outcome measures.Factor analysis of baseline scores yielded two "source factors" (parent and teacher) and one "instrument factor" (parent-child interactions). A composite score was created from the average of standardized parent and teacher measures.The composite was internally consistent (alpha = .83), reliable (test-retest over 3 months = 0.86), and correlated 0.61 with clinician global judgments. In an intent-to-treat analysis, Comb was statistically significantly better than all other treatments, with effect sizes ranging from small (0.28) versus MedMgt, to moderately large (0.70) versus a community comparison group.A composite of ADHD variables may be an important tool in future treatment trials with ADHD and may avoid some of the statistical limitations of multiple measures.

Abstract

To examine ratings and objective measures of attention-deficit/hyperactivity disorder (ADHD) symptoms to assess whether ADHD children with and without comorbid conditions have equally high levels of core symptoms and whether symptom profiles differ as a function of comorbidity and gender.Four hundred ninety-eight children from the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) were divided into comorbid groups based on the parent Diagnostic Interview Schedule for Children and assessed via parents' and teachers' Swanson, Nolan, and Pelham (SNAP) ratings and a continuous performance test (CPT). Comorbidity and gender effects were examined using analyses of covariance controlled for age and site.CPT inattention, impulsivity, and dyscontrol errors were high in all ADHD groups. Children with ADHD + oppositional defiant or conduct disorder were rated as more impulsive than inattentive, while children with ADHD + anxiety disorders (ANX) were relatively more inattentive than impulsive. Girls were less impaired than boys on most ratings and several CPT indices, particularly impulsivity, and girls with ADHD + ANX made fewer CPT impulsivity errors than girls with ADHD-only.Children with ADHD have high levels of core symptoms as measured by rating scales and CPT, irrespective of comorbidity. However, there are important differences in symptomatology as a function of comorbidity and gender.

Abstract

Previous research has been inconclusive whether attention-deficit/hyperactivity disorder (ADHD), when comorbid with disruptive disorders (oppositional defiant disorder [ODD] or conduct disorder [CD]), with the internalizing disorders (anxiety and/or depression), or with both, should constitute separate clinical entities. Determination of the clinical significance of potential ADHD + internalizing disorder or ADHD + ODD/CD syndromes could yield better diagnostic decision-making, treatment planning, and treatment outcomes.Drawing upon cross-sectional and longitudinal information from 579 children (aged 7-9.9 years) with ADHD participating in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA), investigators applied validational criteria to compare ADHD subjects with and without comorbid internalizing disorders and ODD/CD.Substantial evidence of main effects of internalizing and externalizing comorbid disorders was found. Moderate evidence of interactions of parent-reported anxiety and ODD/CD status were noted on response to treatment, indicating that children with ADHD and anxiety disorders (but no ODD/CD) were likely to respond equally well to the MTA behavioral and medication treatments. Children with ADHD-only or ADHD with ODD/CD (but without anxiety disorders) responded best to MTA medication treatments (with or without behavioral treatments), while children with multiple comorbid disorders (anxiety and ODD/CD) responded optimally to combined (medication and behavioral) treatments.Findings indicate that three clinical profiles, ADHD co-occurring with internalizing disorders (principally parent-reported anxiety disorders) absent any concurrent disruptive disorder (ADHD + ANX), ADHD co-occurring with ODD/CD but no anxiety (ADHD + ODD/CD), and ADHD with both anxiety and ODD/CD (ADHD + ANX + ODD/CD) may be sufficiently distinct to warrant classification as ADHD subtypes different from "pure" ADHD with neither comorbidity. Future clinical, etiological, and genetics research should explore the merits of these three ADHD classification options.

Abstract

Using a subsample of 105 children and their parents (100 mothers, 57 fathers) from the Multimodal Treatment Study of Children with ADHD (the MTA), the value of parents' baseline cognitions as predictors of children's treatment outcome at 14 months was examined. Measures of parents' cognitions about themselves, their ADHD children, and their parenting, as well as a self-report measure of dysfunctional discipline were included. Both mothers' and fathers' self-reported use of dysfunctional discipline predicted worse child treatment outcome. Low self-esteem in mothers, low parenting efficacy in fathers, and fathers' attributions of noncompliance to their ADHD child's insufficient effort and bad mood also were associated with worse child treatment outcome. All of these predictive relations were obtained even after MTA treatment effects had been taken into account. Secondary analyses indicated that mothers had a more external locus of control, lower self-esteem, lower parenting efficacy, and a greater tendency to attribute noncompliance to their ADHD child's bad mood than did fathers.

Abstract

To elucidate processes underlying therapeutic change in a large-scale randomized clinical trial, we examined whether alterations in self-reported parenting practices were associated with the effects of behavioral, medication, or combination treatments on teacher-reported outcomes (disruptive behavior, social skills, internalizing symptoms) in children with attention-deficit hyperactivity disorder (ADHD). Participants were 579 children with Combined-type ADHD, aged 7-9.9 years, in the Multimodal Treatment Study of Children with ADHD (MTA). We uncovered 2 second-order factors of parenting practices, entitled Positive Involvement and Negative/Ineffective Discipline. Although Positive Involvement was not associated with amelioration of the school-based outcome measures, reductions in Negative/Ineffective Discipline mediated improvement in children's social skills at school. For families showing the greatest reductions in Negative/Ineffective Discipline, effects of combined medication plus behavioral treatment were pronounced in relation to regular community care. Furthermore, only in combination treatment (and not in behavioral treatment alone) was decreased Negative/Ineffective Discipline associated with reduction in children's disruptive behavior at school. Here, children in families receiving combination treatment who showed the greatest reductions in Negative/Ineffective Discipline had teacher-reported disruptive behavior that was essentially normalized. Overall, the success of combination treatment for important school-related outcomes appears related to reductions in negative and ineffective parenting practices at home; we discuss problems in interpreting the temporal sequencing of such process-outcome linkages and the means by which multimodal treatment may be mediated by psychosocial processes related to parenting.

Abstract

Initial moderator analyses in the Multimodal Treatment Study of Children with ADHD (MTA) suggested that child anxiety ascertained by parent report on the Diagnostic Interview Schedule for Children 2.3 (DISC Anxiety) differentially moderated the outcome of treatment. Left unanswered were questions regarding the nature of DISC Anxiety, the impact of comorbid conduct problems on the moderating effect of DISC Anxiety, and the clinical significance of DISC Anxiety as a moderator of treatment outcome. Thirty-three percent of MTA subjects met DSM-III-R criteria for an anxiety disorder excluding simple phobias. Of these, two-thirds also met DSM-III-R criteria for comorbid oppositional-defiant or conduct disorder whereas one-third did not, yielding an odds ratio of approximately two for DISC Anxiety, given conduct problems. In this context, exploratory analyses of baseline data suggest that DISC Anxiety may reflect parental attributions regarding child negative affectivity and associated behavior problems (unlike fearfulness), particularly in the area of social interactions, another core component of anxiety that is more typically associated with phobic symptoms. Analyses using hierarchical linear modeling (HLM) indicate that the moderating effect of DISC Anxiety continues to favor the inclusion of psychosocial treatment for anxious ADHD children irrespective of the presence or absence of comorbid conduct problems. This effect, which is clinically meaningful, is confined primarily to parent-reported outcomes involving disruptive behavior, internalizing symptoms, and inattention; and is generally stronger for combined than unimodal treatment. Contravening earlier studies, no adverse effect of anxiety on medication response for core ADHD or other outcomes in anxious or nonanxious ADHD children was demonstrated. When treating ADHD, it is important to search for comorbid anxiety and negative affectivity and to adjust treatment strategies accordingly.

Abstract

The aim of this study was to discover clinically useful predictors of attrition and outcome in the treatment of bulimia nervosa with cognitive behavior therapy.Pretreatment, course of treatment, and outcome data were gathered on 194 women meeting the DSM-III-R criteria for bulimia nervosa who were treated with 18 sessions of manual-based cognitive behavior therapy in a three-site study. Differences between dropouts and nondropouts and between recovered and nonrecovered participants were first examined descriptively, and signal detection analyses were then used to determine clinically significant cutoff points predicting attrition and abstinence.The dropouts were characterized by more severe bulimic cognitions and greater impulsivity, but it was not possible to identify clinically useful predictors. The participants with treatment failures were characterized by poor social adjustment and a lower body mass index, presumably indicating greater dietary restriction. However, early progress in therapy best predicted outcome. Signal detection analyses revealed that poor outcome was predicted by a reduction in purging of less than 70% by treatment session 6, allowing identification of a substantial proportion of prospective failures.A cutoff point based on reduction of purging by session 6 usefully differentiates patients who will and will not respond to cognitive behavior therapy for bulimia nervosa, potentially allowing early use of a second therapy.

Abstract

Considerable research has been devoted to the hypothalamic-pituitary-adrenal (HPA) axis in depression, but relatively little attention has been given to intensive monitoring of hormone secretion over time. Such research is potentially important because the HPA axis has prominent circadian and ultradian periodicity. Comparison of depressed patients with and without psychotic features is also important because HPA axis abnormalities may be especially pronounced in psychotic depressed patients.Eleven patients with psychotic major depression (PMD patients), 38 patients with nonpsychotic major depression (NPMD patients), and 33 healthy control subjects, all drug free, were studied. Patients with PMD and NPMD were outpatients recruited primarily by advertisement. Subjects were admitted to a General Clinical Research Center and had blood drawn through an intravenous line for determination of cortisol and corticotropin (ACTH) levels every hour for 24 hours.Among NPMD patients, the 24-hour cortisol amplitude was significantly (P =.02) reduced in comparison with control subjects, while ACTH indices did not differ between NPMD patients and the control group. Among PMD patients, the ACTH 24-hour mean was significantly (P =.03) increased compared with controls, while PMD patients and the control group did not differ significantly in cortisol indices.In the population studied, PMD and NPMD patients have distinct profiles of HPA axis dysregulation.

Abstract

Perinatal medical illness has been associated with child maltreatment. Using a Child Protective Service (CPS) report as the defining event, this study explores to what extent perinatal morbidity is a risk factor for maltreatment.Medical charts of 206 children ages 0-3 years were reviewed. Data regarding birth history were collected and analyzed in three groups of children: children whose medical record indicated a report to CPS based on prenatal findings (Early Maternal Inadequacy group [EMI]), children whose medical record indicated a report to CPS based only on postnatal findings (Child Maltreatment group [CM]), and a control group without CPS report (NM).Compared to the CM and the NM groups, children in the EMI group showed significantly lower birth weight and higher neonatal morbidity as measured by Apgar scores, frequency of oxygen requirement and intubation at birth, frequency of admission to Neonatal Intensive Care unit, and frequency of neonatal medical problems. There was no significant difference between the CM and the NM groups in birth weight, gestational age, and other measures of morbidity.The results of the study suggest that perinatal complications are associated with prenatal maltreatment. Previously reported strong associations between neonatal morbidity and child abuse are more likely a result of antecedent prenatal maternal behaviors (early maternal inadequacy). Early maternal inadequacy, a clinically and demographically distinct phenomenon, is important due to serious health, development and financial implications and deserves further exploration.

Abstract

The Apolipoprotein-E (APOE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and cognitive decline in older adults. Depression may also be a risk factor for dementia, and depression is important in the differential diagnosis of dementia. The authors performed a 5-year longitudinal study of APOE genotype and change in Geriatric Depression Scale scores in 113 community-dwelling older adults. No association was observed between APOE genotype and change in depressive symptoms. These results do not support the hypothesis that the APOE epsilon 4 allele is associated with depression. Important objections have been raised to APOE genotyping in the diagnosis of AD. However, the specificity of APOE genotyping in AD diagnosis would not appear to be compromised by an association with depression.

Abstract

: Abnormal circadian rhythms have been observed in patients with cancer, but the prognostic value of such alterations has not been confirmed. We examined the association between diurnal variation of salivary cortisol in patients with metastatic breast cancer and subsequent survival. We explored relationships between cortisol rhythms, circulating natural killer (NK) cell counts and activity, prognostic indicators, medical treatment, and psychosocial variables.Salivary cortisol levels of 104 patients with metastatic breast cancer were assessed at study entry at 0800, 1200, 1700, and 2100 hours on each of 3 consecutive days, and the slope of diurnal cortisol variation was calculated using a regression of log-transformed cortisol concentrations on sample collection time. NK cell numbers were measured by flow cytometry, and NK cell activity was measured by the chromium release assay. The survival analysis was conducted by the Cox proportional hazards regression model with two-sided statistical testing.Cortisol slope predicted subsequent survival up to 7 years later. Earlier mortality occurred among patients with relatively "flat" rhythms, indicating a lack of normal diurnal variation (Cox proportional hazards, P =. 0036). Patients with chest metastases, as opposed to those with visceral or bone metastases, had more rhythmic cortisol profiles. Flattened profiles were linked with low counts and suppressed activity of NK cells. After adjustment for each of these and other factors, the cortisol slope remained a statistically significant, independent predictor of survival time. NK cell count emerged as a secondary predictor of survival.Patients with metastatic breast cancer whose diurnal cortisol rhythms were flattened or abnormal had earlier mortality. Suppression of NK cell count and NK function may be a mediator or a marker of more rapid disease progression.

Abstract

Research suggests that cognitive-behavioral therapy (CBT) is the most effective psychotherapeutic treatment for bulimia nervosa. One exception was a study that suggested that interpersonal psychotherapy (IPT) might be as effective as CBT, although slower to achieve its effects. The present study is designed to repeat this important comparison.Two hundred twenty patients meeting DSM-III-R criteria for bulimia nervosa were allocated at random to 19 sessions of either CBT or IPT conducted over a 20-week period and evaluated for 1 year after treatment in a multisite study.Cognitive-behavioral therapy was significantly superior to IPT at the end of treatment in the percentage of participants recovered (29% [n=32] vs 6% [n=71), the percentage remitted (48% [n=53] vs 28% [n = 31]), and the percentage meeting community norms for eating attitudes and behaviors (41% [n=45] vs 27% [n=30]). For treatment completers, the percentage recovered was 45% (n= 29) for CBT and 8% (n= 5) for IPT. However, at follow-up, there were no significant differences between the 2 treatments: 26 (40%) CBT completers had recovered at follow-up compared with 17 (27%) IPT completers.Cognitive-behavioral therapy was significantly more rapid in engendering improvement in patients with bulimia nervosa than IPT. This suggests that CBT should be considered the preferred psychotherapeutic treatment for bulimia nervosa.

Use of placebo control groups in evaluating efficacy of treatment of unipolar major depressionSchatzberg, A. F., Kraemer, H. C.ELSEVIER SCIENCE INC.2000: 736-744

Abstract

Double-blind, random-assignment placebo-controlled trials are routinely used in evaluating efficacy of potential antidepressant agents. In recent years concern has risen that placebo response rates in unipolar depression are too high, and this has eroded confidence in both old and new agents. At the same time, the use of placebos has been questioned by patients and their advocates. We review factors that have been commonly explored as associated with placebo response (e.g., length of episode, severity, subtype), as well as issues in methodology (e.g., interrater reliability, statistical artifacts). We discuss possible methods of dealing with the problem of placebo response, emphasizing reconceptualizing effect sizes to design more powerful single trials and a systematic sequence of trials to achieve the right answers.

Abstract

In order to begin to compensate for a lack of data on the effects of athletic participation in the development of adolescent mental health patterns, as well as to assess general health of the adolescent population, the Juvenile Wellness and Health Inventory (JWHS-76) was administered to 1,769 high school students. Our results indicate that sports participation is associated with self-reported lower total risk scores, mental and physical health benefits, and an increased risk of injury. This suggests a positive role for organized sports participation in youth populations. Prospective studies are needed to assess the impact of different sports, mounting performance pressure, and transition into collegiate levels of participation.

Abstract

Cross-sectional studies are often used in psychiatric research as a basis of longitudinal inferences about developmental or disease processes. While the limitations of such usage are often acknowledged, these are often understated. The authors describe how such inferences are often, and sometimes seriously, misleading.Why and how these inferences mislead are here demonstrated on an intuitive level, by using simulated data inspired by real problems in psychiatric research.Four factors with major roles in the relationship between cross-sectional studies and longitudinal inferences are selection of time scale, type of developmental process studied, reliability of measurement, and clarity of terminology. The authors suggest how to recognize inferential errors when they occur, describe how to protect against such errors in future research, and delineate the circumstances in which only longitudinal studies can answer crucial questions.The simple conclusion is that one must always use the results of cross-sectional studies to draw inferences about longitudinal processes with trepidation.

Abstract

To identify risk factors for onset of panic attacks in adolescents, a prospective cohort design was used to evaluate the following risk factors: negative affectivity, female sex, anxiety sensitivity, and childhood separation anxiety disorder. These risk factors were also evaluated for predicting onset of major depression to test their specificity.The sample consisted of 2,365 high school students assessed over a 4-year period. Assessments included self-report questionnaires and structured clinical interviews. Cox proportional hazards models were used to evaluate risk.Consistent with previous studies, prior major depression predicted onset of panic attacks and a history of panic attacks predicted onset of major depression. After adjusting for the effects of prior major depression, negative affectivity and anxiety sensitivity, but not female sex or childhood separation anxiety disorder, predicted onset of 4-symptom panic attacks. However, female sex and negative affectivity but not anxiety sensitivity or childhood separation anxiety disorder predicted onset of major depression after adjustment for the effects of prior panic attacks.Negative affectivity appears to be a nonspecific risk factor for panic attacks and major depression, whereas anxiety sensitivity appears to be a specific factor that increases the risk for 4-symptom panic attacks in adolescents.

Abstract

This article discusses common pitfalls of multisite randomized clinical trials of efficacy and effectiveness. Issues considered include (1) premature initiation, (2) ineffective study structure, (3) too much or too little communication among researchers, (4) neglect of site differences, (5) use of "naked" p values, (6) premature closure, and (7) overreliance on the interpretation and memory of individual researchers. If future researchers are aware of these common pitfalls, they may be able to avoid them.

Abstract

Three sites collaborated to evaluate the reliability and validity of 2 measures, developed in tandem to assess symptomatology and impairment in 4- to 8-year-old children: the Berkeley Puppet Interview Symptomatology Scales (BPI-S) and the Health and Behavior Questionnaire (HBQ).In this case-control study, mothers, teachers, and children reported on multiple dimensions of children's mental health for 120 children (67 community and 53 clinic-referred children).The BPI-S and the parent and teacher versions of the HBQ demonstrated strong test-retest reliability and discriminant validity on a majority of symptom scales. Medium to strong effect sizes (Cohen d) indicated that children in the clinic-referred group were viewed by all 3 informants as experiencing significantly higher levels of symptomatology than nonreferred, community children.The availability of a set of multi-informant instruments that are psychometrically sound, developed in tandem, and developmentally appropriate for young children will enhance researchers' ability to investigate and understand symptomatology or the emergence of symptomatology in middle childhood.

Abstract

Intent-to-treat analyses of the study revealed that medication management, alone or combined with intensive behavioral treatment, was superior to behavioral treatment and community care in reducing attention-deficit/hyperactivity disorder (ADHD) symptoms; but only combined treatment showed consistently greater benefit than community care across other outcome domains (disruptive and internalizing symptoms, achievement, parent-child relations, and social skills). We examine response patterns in subgroups defined by baseline variables (moderators) or variables related to treatment implementation (mediators).We reconducted random-effects regression (RR) analyses, adding factors defined by moderators (sex, prior medication use, comorbid disruptive or anxiety disorder, and public assistance) and a mediator (treatment acceptance/attendance).Study outcomes (N = 579) were upheld in most moderator subgroups (boys and girls, children with and without prior medication, children with and without comorbid disruptive disorders). Comorbid anxiety disorder did moderate outcome; in participants without anxiety, results paralleled intent-to-treat findings. For those with anxiety disorders, however, behavioral treatment yielded significantly better outcomes than community care (and was no longer statistically different from medication management and combined treatment) regarding ADHD-related and internalizing symptoms. In families receiving public assistance, medication management yielded decreased closeness in parent-child interactions, and combined treatment yielded relatively greater benefits for teacher-reported social skills. In families with high treatment acceptance/attendance, intent-to-treat results were upheld. Acceptance/attendance was particularly important for medication treatments. Finally, two thirds of children given community care received stimulants. Behavioral treatment did not significantly differ from, but medication management was superior to, this subgroup.Exploratory analyses revealed that our study (the Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder [MTA]) results were confirmed across most baseline variables and treatment acceptance/attendance. In children with ADHD plus anxiety, behavioral treatment surpassed community care and approached medication-based treatments regarding parent-reported ADHD symptoms.

Abstract

A prospective clinical trial was conducted.To determine the feasibility of removing activity restrictions after surgery and encouraging early return to work; to ascertain the clinical and behavioral response to such a strategy; and to identify factors predictive of early return to work, preparatory to possible randomized clinical trials.Current practice usually entails several weeks to several months of restricted activities after lumbar discectomy to avoid disc "reinjury." Earlier work has suggested these restrictions may not be necessary.One hundred fifty-two consecutive working patients undergoing limited open discectomy for herniated lumbar intervertebral disc were treated postoperatively with no activity restrictions. Patients were encouraged to return to full activities as soon as possible. The patients were followed for a minimum of 2 years (average follow-up time = 4.8 years). At follow-up, an independent examiner evaluated each patient and collected further postoperative data.One hundred forty-nine of the 152 patients (98%) returned to work. The average work loss was 1.2 weeks and 148 of 149 patients had returned to full duty by 8 weeks. Approximately one-third of the group returned to work within 1 week of surgery (32%), many the next day. Statistical analysis demonstrated very early return to work did not correlate with either recurrent sciatica, reoperation for reherniation, or ultimate clinical outcome. Seventeen patients (11.2%) had possible reherniations (recurrent sciatica) and eight underwent reoperation (5.3%).Lifting of postoperative activity restrictions after limited discectomy allowed shortened time to return to work relative to the 4 to 16 weeks commonly recommended. Complication rates appear comparable to those reported in the literature for patients under postoperative restrictions. Postoperative restrictions may not be necessary in most patients.

Abstract

Chromosomal region 15q11-q13 has been implicated to harbor a susceptibility gene or genes underlying autism. Evidence has been derived from the existence of cytogenetic anomalies in this region associated with autism, and the report of linkage in a modest collection of multiplex families. Most recently, linkage disequilibrium with the marker GABRB3-155CA2 in the candidate locus GABRB3, located in this region, has been reported. We searched for linkage using eight microsatellite markers located in this region of chromosome 15 in 147 affected sib-pairs from 139 multiplex autism families. We also tested for linkage disequilibrium in the same set of families with the same markers. We found no evidence for excess allele sharing (linkage) for the markers in this region. Also, we found no evidence of linkage disequilibrium, including for the locus GABRB3-155CA2. Thus, it appears that the role of this region of chromosome 15 is minor, at best, in the majority of individuals with autism.

Abstract

To identify profiles of subjects who respond to mnemonic training for serial word and proper name recall.Analysis of J. O. Brooks et al.'s (1999) mnemonic training data using Quality Receiver Operating Characteristic (QROC) and longitudinal regression analyses (LRA).Community.224 community-dwelling adults 55 years of age and older who wished to improve their memory.Performance on serial word and proper name tests; performance on cognitive ability tests.Although the QROC and LRA identified several common predictors (baseline performance, mental rotation ability, and paired associate learning), the QROC identified additional predictors and cognitive ability profiles associated with successful response.Similar degrees of response to mnemonic training are associated with heterogeneous cognitive profiles. This finding highlights the fact that participants rely on a variety of abilities to derive benefit from mnemonic training and thus suggests different avenues from which to approach this training.

Abstract

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying =10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Abstract

Case series and follow-up studies suggest that clozapine may have mood-stabilizing properties in addition to antipsychotic action in patients with schizoaffective disorder, bipolar type, and bipolar I disorder, but the generalizability of these findings is limited. This article describes a randomized, open study of clozapine add-on therapy versus treatment as usual for patients with treatment-resistant illness and a history of mania.Thirty-eight patients meeting the DSM-IV criteria for schizoaffective or bipolar disorder that was deemed treatment-resistant were randomly assigned to clozapine add-on treatment (N = 19) or treatment as usual (no clozapine) (N = 19) and followed up for 1 year. Patients received monthly ratings on the Brief Psychiatric Rating Scale, Clinical Global Impression scale, Bech-Rafaelsen Mania Scale, Hamilton Depression Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Abnormal Involuntary Movement Scale, and a 40-item side effect checklist. Differences between treatment groups were assessed according to a pattern-mix random-regression model. An additional analysis compared group differences in rating scale scores against relative time in the study.Significant between-group differences were found in scores on all rating scales except the Hamilton depression scale. Total medication use over 1 year significantly decreased in the clozapine group. No significant differences between groups in somatic complaints were noted. The subjects with nonpsychotic bipolar I disorder who received clozapine showed a degree of improvement similar to that of the entire clozapine-treated group. Clozapine dose was significantly higher for the patients with schizoaffective illness than for those with bipolar disorder.The results of this study support clozapine's independent mood-stabilizing property. They demonstrate that clozapine use was associated with significant clinical improvement relative to treatment as usual.

Abstract

Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.

Ethnic variation in cardiovascular disease risk factors among children and young adults - Findings from the Third National Health and Nutrition Examination Survey, 1988-1994JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATIONWinkleby, M. A., Robinson, T. N., Sundquist, J., Kraemer, H. C.1999; 281 (11): 1006-1013

Abstract

Knowledge about ethnic differences in cardiovascular disease (CVD) risk factors among children and young adults from national samples is limited.To evaluate ethnic differences in CVD risk factors, the age at which differences were first apparent, and whether differences remained after accounting for socioeconomic status (SES).Third National Health and Nutrition Examination Survey, 1988-1994.Eighty-nine mobile examination centers.A total of 2769 black, 2854 Mexican American, and 2063 white (non-Hispanic) children and young adults aged 6 to 24 years.Ethnicity and household level of education (SES) in relation to body mass index (BMI), percentage of energy from dietary fat, cigarette smoking, systolic blood pressure, glycosylated hemoglobin (HbA1c), and non-high-density lipoprotein cholesterol (non-HDL-C [the difference between total cholesterol and HDL-C]).The BMI levels were significantly higher for black and Mexican American girls than for white girls, with ethnic differences evident by the age of 6 to 9 years (a difference of approximately 0.5 BMI units) and widening thereafter (a difference of >2 BMI units among 18- to 24-year-olds). Percentages of energy from dietary fat paralleled these findings and were also significantly higher for black than for white boys. Blood pressure levels were higher for black girls than for white girls in every age group, and glycosylated hemoglobin levels were highest for black and Mexican American girls and boys in every age group. In contrast, smoking prevalence was highest for white girls and boys, especially for those from low-SES homes (77% of young men and 61% of young women, aged 18-24 years, from low-SES homes were current smokers). All ethnic differences remained significant after accounting for SES and age.These findings show strong ethnic differences in CVD risk factors among youths of comparable age and SES from a large national sample. The differences highlight the need for heart disease prevention programs to begin early in childhood and continue throughout young adulthood to reduce the risk of atherosclerosis.

Abstract

We examined relationships between demographic and diagnostic variables and Benton Visual Retention Test performance in older adults aged 55 to 97 years. We derived extended geriatric norms for BVRT total number correct scores adjusted for variables that contributed significantly to the variance. We also investigated BVRT performance in two commonly presenting diagnostic groups: (1) normal adults with memory concerns, and (2) a group with mixed neurologic disorders. Age and education but not gender were significantly associated with BVRT performance in both normals and normals with memory concerns. Level of cognitive deficit was a moderating factor in that age and education also contributed significantly to the BVRT performance of no/low deficit neurologic patients but had no impact in patients whose cognitive deficits were moderate/severe.

Abstract

This study extends the results of a large randomized clinical trial of a multicomponent in-hospital smoking cessation intervention for general hospitalized smokers by examining subgroups of patients who responded to the intervention. The results, obtained using signal detection analysis, produced 6 subgroups of patients with varying degrees of intervention responsiveness. The subgroup most responsive was marked by 100% confidence to quit smoking at baseline. Among patients with less than 100% confidence, confidence interacted with age, depressed mood scores, addiction scores, and alcohol intake to discriminate 5 additional subgroups. Discussion focuses on how this information can be used in clinical decision making to treat subpopulations of smokers and directs attention to possible areas of underlying biopsychosocial processes that may interact to affect successful long-term cessation.

Abstract

Our goal was to validate a self-administered narcolepsy questionnaire focusing on cataplexy. Nine hundred and eight three consecutive subjects entering the Stanford Sleep Disorder Clinic completed the questionnaire. Clinic physicians reported on the presence or absence of "clear-cut" cataplexy. Responses to 51 cataplexy-related questionnaire items were compared between subjects with clear-cut cataplexy (n = 63) and all other patients (n = 920). As previously reported, a large portion of the non-narcoleptic population was found to experience muscle weakness with various intense emotions (1.8% to 18.0%) or athletic activities (26.2% to 28.8%). Factor analysis and Receiver Operating Characteristic Curve (ROC) analysis were used to determine the most predictive items for clear-cut cataplexy. Most strikingly, cataplexy was best differentiated from other types of muscle weakness when triggered by only three typical situations: "when hearing and telling a joke," "while laughing," or "when angry." Face or neck, rather than limbs, were also more specifically involved in clear-cut cataplexy. Other items, such as length of attacks, bilaterality, and alteration in consciousness, were poorly predictive. A simple decision tree was constructed to isolate high-(91.7%) and low-(0.6%) risk groups for cataplexy. This questionnaire will be used to increase diagnostic consistency across clinical centers, thus providing more homogenous subject pools for clinical and basic research studies.

Abstract

Little is known about pathways by which socioeconomic status (SES) translates into individual differences in cardiovascular disease (CVD) risk factors. Because the socioeconomic structure is not the same for all ethnic subgroups, the pathways that lead to the development of CVD risk factors may vary by both SES and ethnicity. We used data from a large national survey to examine the independent associations of two indicators of SES (education and income) and ethnicity with six primary CVD risk factors. We then used data on smoking that reflected a temporal sequence to examine the extent to which SES and ethnicity influenced smoking at three different time points, from smoking onset, to a serious quit attempt, to successful quitting. These analyses provide an understanding of the relationships between SES, ethnicity, and CVD risk factors and suggest that if the timing, focus, and content of intervention programs take pathways into account they will result in more successful outcomes.

Abstract

Behavioral inhibition in children has been hypothesized to be a risk factor for the later development of social phobia. However, this hypothesis has yet to be demonstrated in a prospective study. The purpose of the study presented here is to test whether behavioral inhibition in childhood constitutes a risk factor for social phobia during adolescence.The sample consisted of 2,242 high school students assessed over a 4-year period. Assessments included self-report questionnaires, structured clinical interviews, and measurements of heart rate. Cox proportional hazards models were used to evaluate risk.Social avoidance, a component of behavioral inhibition, predicted onset of social phobia during high school. However, social avoidance was not related to depression in adolescence. Another component of behavioral inhibition, fearfulness, increased the risk for both social phobia and depression. Among subjects who were both socially avoidant and fearful, 22.3% developed social phobia--a risk more than four times greater than that for subjects with neither feature of behavioral inhibition.This prospective study demonstrates that behavioral inhibition in childhood increases the risk of social phobia in adolescence.

Abstract

This study investigated whether the Apolipoprotein (APOE) epsilon4 allele was associated with cognitive decline in community-dwelling older adults.Longitudinal cognitive performance of older adults with the epsilon3/epsilon4 genotype was compared with that of older adults with the epsilon3/epsilon3 genotype.Aging Clinical Research Center, Stanford University.One hundred community-dwelling older adults were recruited from a pool of 531 individuals who had participated in a memory training study 4 to 5 years earlier. These individuals were concerned about their memory functioning and were recruited through newspaper advertisements and contacts with local senior centers. The 100 individuals who agreed to participate in the follow-up investigation were between 59 and 95 years of age.At both baseline and follow-up, subjects were administered a battery of seven cognitive tests that examined verbal and spatial memory, attention, speed-of-processing, and language abilities. APOE genotype was determined at follow-up.Individuals with the epsilon3/epsilon4 APOE genotype were significantly younger than individuals with the APOE epsilon3/epsilon3 genotype. No significant differences were observed between the two groups on measures of attention, speed-of-processing, vocabulary, immediate verbal memory, and immediate spatial memory. However, those older adults with the epsilon3/epsilon4 genotype exhibited significantly greater decline in performance on delayed recall of verbal material than did those with the epsilon3/epsilon3 APOE genotype.These findings are consistent with previous studies, which suggest that the APOE epsilon4 allele predicts decline on measures of delayed recall.

Abstract

'Stages', as used in clinical practice and research, are defined, their value described, and criteria are proposed for their evaluation. The specific interest is in staging Alzheimer's disease (AD). Two staging systems, one based on the Global Deterioration Scale (GDS) and one based on the Mini-Mental State Exam (MMSE), are compared in terms of these criteria, as an illustration of the process involved. We propose that there is not one unique staging system, that different staging criteria might be appropriate to different research or clinical needs, depending on which part of the temporal course of the disease is of primary interest, and on whether the focus is on cognitive, functional, neurological, behavioral, economic, or other issues. GDS staging seems a better choice for the later stages of AD when the focus is on functional change. MMSE staging seems a better choice for tracking the earlier stages of AD when the focus is on cognitive change.

Abstract

Cardiovascular disease (CVD) risk factors are higher among ethnic minority women than among white women in the United States. However, because ethnic minority women are disproportionately poor, socioeconomic status (SES) may substantially explain these risk factor differences.To determine whether differences in CVD risk factors by ethnicity could be attributed to differences in SES.Third National Health and Nutrition Examination Survey conducted between 1988 and 1994.Eighty-nine mobile examination centers.A total of 1762 black, 1481 Mexican American, and 2023 white women, aged 25 to 64 years, who completed both the home questionnaire and medical examination.Ethnicity and years of education (SES) in relation to systolic blood pressure, cigarette smoking, body mass index (BMI, a measure of weight in kilograms divided by the square of height in meters), physical inactivity, non-high-density lipoprotein cholesterol (non-HDL-C [the difference between total cholesterol and HDL-C]), and non-insulin-dependent diabetes mellitus.As expected, most CVD risk factors were higher among ethnic minority women than among white women. After adjusting for years of education, highly significant differences in blood pressure, BMI, physical inactivity, and diabetes remained for both black and Mexican American women compared with white women (P

Abstract

This study examined the association of weight concerns with potential risk factors for the development of eating disorders.A self-report survey was given to 103 elementary (Grades 4 and 5) and 420 middle (Grades 6-8) school students in Arizona and California. Of these, 78 elementary and 333 middle school students provided complete data and were used in the analyses.In a multivariate stepwise regression analysis, the importance that peers put on weight and eating was most strongly related to weight concerns in the elementary school girls, accounting for 34% of the variance after adjusting for site differences. Trying to look like girls/women on TV and in magazines as well as body mass index (BMI) entered the final model that accounted for 57% of the variance in weight concerns. In middle school, the importance that peers place on weight and eating was also the strongest predictor accounting for 33% of the variance followed by confidence, BMI, trying to look like girls/women on TV and in magazines, and being teased about weight. Together these variables accounted for 55% of the variance.Prevention programs aimed at reducing weight concerns need to address these factors.

Abstract

To examine the trade-offs among clinical, targeted, and universal interventions aimed at lowering the burden of suffering from child psychiatric disorders.Data from clinical and research studies were organized to show the advantages and disadvantages of the three strategies.Important trade-offs exist among these three approaches. The strategy to reduce the burden of suffering from child psychiatric disorder should consist of a number of concurrent steps. First, effective universal programs should be in place. Targeted programs should follow for those not helped sufficiently by the universal programs. Finally, for those unaffected by the targeted programs, clinical services should be available.An optimal mix of universal, targeted, and clinical programs is needed. The nature of the combination will change as knowledge accumulates, and there will always be trade-offs among these three. Acad.

Abstract

This article reports cross-sectional and follow-up data with actigraphic measures of nocturnal sleep and rest/activity in 61 Alzheimer's disease (AD) patients as well as the relation of actigraphic measures to levels of behavioral disturbance across different stages of the disease. Over the course of approximately 1.5 years' follow-up, patients showed significant deterioration of nocturnal sleep parameters, but no significant change in rest/activity circadian rhythm parameters. There were also significant correlations among nocturnal sleep, rest/activity circadian rhythm, and behavioral disturbance measures, but only in relatively early stages of AD. It is argued that study of nocturnal sleep and circadian rhythm in relation to behavioral disturbance in AD requires longitudinal data and analyses that take into account the stage of disease at which patients are assessed.

Abstract

The question of whether Mini-Mental State Examination scores should be adjusted for age and educational levels to screen for dementia in clinical populations is reexamined in the results of a recent study supporting adjustment. If the criterion is to identify the most accurate screening procedure for each sociodemographic subgroup, the evidence indicates that the unadjusted scores are preferable. Other criteria might lead to different conclusions. The validities of some of these criteria are questionable because they have the flaw that they are easily satisfied by using random decision procedures.

Abstract

While monotherapy has significant limitations in bipolar disorder, few published data addressing alternatives exist. Treatment algorithms have been proposed, but none have undergone empirical evaluation. This study provides a systematic prospective, open evaluation of the effectiveness and tolerability of a treatment algorithm for patients with histories of mania.Twenty-eight symptomatic outpatients from a public mental health facility who were diagnosed as having either bipolar I or schizoaffective illness, bipolar type, entered the study. Minimum blood levels of lithium and divalproex sodium were defined. Medications were pushed to predetermined levels (as tolerated) before proceeding to the next algorithm step. Clinical symptoms were assessed monthly using the Brief Psychiatric Rating Scale (BPRS, 27 item) and Clinical Global Impressions scale.Pretreatment and posttreatment clinical symptoms were compared. Over 50% of patients attained 30% improvement from baseline BPRS after 4 months. Thirty-six percent of patients (N = 10) became mood stable, 46% (N = 13) remained mood unstable, and 18% (N = 5) dropped out before completing the algorithm. Although patients who finished the algorithm were taking more medication, either dosage and/or drugs, somatic complaints did not increase.The potential benefit of a defined treatment algorithm was demonstrated for these complex and persistently ill patients. Despite long treatment histories, patients improved with more frequent visits and addition of medication(s). A randomized controlled trial comparing a similar treatment algorithm with treatment-as-usual is warranted.

Abstract

Signal detection methods were used to identify predictors of successful weight loss in 177 mildly to moderately overweight women and men assigned to one of two weight-loss programs. Predictors included initial demographic, physiological, behavioral, and psychosocial characteristics, and program type (e.g. diet-only and diet-plus-exercise). Successful weight loss was defined as a loss of at least two units of body mass index at one year. Four subgroups were identified. Participants in the diet-plus-exercise program who were initially more satisfied with their bodies and did not have a history of repeated weight loss were most likely to succeed (63% succeeded). In contrast, participants assigned to the diet-plus-exercise program who were either extremely dissatisfied with their bodies or who had a history of repeated weight loss were at similar risk for failure as participants in the diet-only program (only 26% to 35% succeeded). The results underscore the potential utility of exploring these subgroups further to inform the development of new treatment strategies to increase the likelihood of success.

Abstract

This paper identifies factors that predict achievement of a low-fat diet among 242 California adults with low literacy skills, following their participation in the Stanford Nutrition Action Program (SNAP), a randomized classroom-based nutrition intervention trial (1993-1994).The intervention classes received a newly developed curriculum that focuses on reducing dietary fat intake (SNAP); the control classes received an existing general nutrition (GN) curriculum. Data were collected at baseline and 3 months postintervention. This hypothesis-generating analysis uses a signal detection method to identify mutually exclusive groups that met the goal of a low fat diet, defined as < 30% of calories from total fat, at 3 months postintervention.Three mutually exclusive groups were identified. Twenty-three percent of Group 1, participants with high baseline dietary fat (> 60 g) who received either the GN or the SNAP curriculum, met the postintervention goal of < 30% of calories from total fat. Thirty-four percent of Group 2, participants with moderate baseline dietary fat (< or = 60 g) who received the GN curriculum, were successful. Sixty percent of Group 3, participants with moderate baseline dietary fat who received the SNAP curriculum, were successful. Members of Group 3 also significantly increased their intake of vegetables, grains, and fiber.Within this population of adults with low literacy skills, a large proportion of those with moderate baseline dietary fat who participated in the SNAP classes met the postintervention criteria for a low-fat diet. A much smaller proportion of those with high baseline dietary fat were successful, suggesting that this group may benefit from different, more intensive, or longer-term interventions.

Abstract

The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first child multisite cooperative agreement treatment study of children conducted by the National Institute of Mental Health, Rockville, Md. It examines the long-term effectiveness of medication vs behavioral treatment vs both for treatment of ADHD and compares state-of-the-art treatment with routine community care. In a parallel-groups design, 576 children (age, 7-9 years) with ADHD (96 at each site) are thoroughly assessed and randomized to 4 conditions: (1) medication alone, (2) psychosocial treatment alone, (3) the combination of both, (4) or community comparison. The first 3 groups are treated for 14 months and all are reassessed periodically for 24 months. Designers met the following challenges: framing clinically relevant primary questions; defining the target population; choice, intensity, and integration and combination of treatments for fair comparisons; combining scientific controls and standardization with clinical flexibility; and implementing a controlled clinical trial in a nonclinical setting (school) controlled by others. Innovative solutions included extensive decision algorithms and manualized adaptations of treatments to specific needs.

Abstract

Signal detection methodology was used to identify the best combination of predictors of long-term exercise adherence in 269 healthy, initially sedentary adults ages 50-65 years. Less educated individuals who were assigned to supervised home-based exercise of either higher or lower intensity and who were less stressed and less fit at baseline than other individuals had the greatest probability of successful adherence by the 2nd year. Overweight individuals assigned to a group-based exercise program were the least likely to be successful 2 years later. Predictors of short-term (1-year) adherence were generally similar to predictors of 2-year adherence. Signal detection analysis may be useful for identifying subgroups of people at risk for underadherence who subsequently might be targeted for intervention.

Abstract

To determine whether neurological and psychiatric symptoms predict survival time among patients with Alzheimer disease (AD) after adjusting for the influence of sociodemographic variables, health conditions, and dementia severity separately for men and women.The sample consisted of 936 men and women diagnosed as having probable or possible AD at 1 of 7 Alzheimer's Disease Diagnostic and Treatment Centers throughout California from 1986 through 1990. Data on dementia severity, comorbid conditions, and demographic characteristics were collected at the time of AD diagnosis. Data on vital status and dates of death were obtained by linking the patient file to several administrative databases maintained by the California State and federal governments. The mean length of follow-up was 31 months. Data were analyzed with Kaplan-Meier survival curves and Cox proportional hazards models.Men had shorter survival times than did women (log-rank test, 30.93, P < .001). Among men, but not women, survival times were negatively associated with selected neurological and psychiatric symptoms. Among women, but not men, a history of cardiovascular conditions was associated with poorer survival.Patterns of survival and predictors of survival time among patients with AD differ by sex. Future studies of survival and progression of AD need to examine men and women separately.

Abstract

The relationship between number of apolipoprotein E epsilon 4 (APOE epsilon 4) alleles and the rate of cognitive decline in patients with Alzheimer's disease was examined.Rate of decline in score on the Mini-Mental State was measured during the active phase of the decline curve between Mini-Mental State scores of 23 and 0. To characterize onset, the authors also estimated for each subject the age at which the Mini-Mental State score fell below 23 and obtained a retrospective report of age at onset from the caregiver. The number of APOE epsilon 4 alleles carried by each subject was determined from genomic DNA samples. The study included 86 subjects with probable Alzheimer's disease who had had at least two cognitive evaluations (a mean of 5.6 evaluations per subject over an average period of 3.6 years).The results did not support an association between APOE epsilon 4 dosage and rate of cognitive decline. Age at onset and age at which the Mini-Mental State score fell below 23 were also not related to APOE epsilon 4 dosage. The APOE allele frequencies were similar to those in other studies of subjects with Alzheimer's disease, showing an enrichment of the epsilon 4 allele.Although the APOE epsilon 4 allele is a risk factor for Alzheimer's disease, there is no support of a strong association between APOE epsilon 4 dosage and rate of cognitive decline. The epsilon 4 allele did not predict age at onset. Methodological inconsistencies may account for discrepancies between these results and previous findings.

Abstract

Terms such as risk, risk factors, and especially the term cause are inconsistently and imprecisely used, fostering scientific miscommunication and misleading research and policy. Clarifying such terms is the essential first step. We define risk and a risk factor (protective factor) and their potency, set out the conceptual basis of the methods by which risk factors are identified and potency demonstrated, and propose criteria for establishing the status of a risk factor as a fixed or variable marker or a causal risk factor. All definitions are based on the state of scientific knowledge (empirical documentation), rather than on hypotheses, speculations, or beliefs. We discuss common approaches and pitfalls and give a psychiatric research example. Imprecise reports can impede the search for understanding the cause and course of any disease and also may be a basis of inadequate clinical or policy decision-making. The issues in risk research are much too important to tolerate less than precise terminology or the less than rigorous research reporting that results from imprecise and inconsistent terminology.

Abstract

This study prospectively evaluated the relationship between early puberty and the onset of internalizing symptoms and disorders in adolescent girls.The sample was drawn from 1,463 sixth-, seventh-, and eighth-grade girls who participated in a longitudinal school-based study of growth and development. Pubertal stage was determined by self-assessment of Tanner stage. Psychiatric assessments included self-report instruments and structured diagnostic interviews. Survival methods were utilized for data analysis.Girls with onset of internalizing symptoms were on average 5 months earlier in pubertal development than those who were asymptomatic (p < .001). In addition, girls with earlier maturation (earliest quartile) were more likely to develop internalizing symptoms than were nonearly matures (hazard ratio = 1.8, confidence interval = 1.2, 2.7). In a subsample of girls followed into high school, early-maturing girls were at marginally higher risk (p < .10) for developing internalizing disorders by the study's end. The highest risk for internalizing disorders was for those girls with both early puberty and prior internalizing symptoms (odds ratio = 3.3).Early puberty increases the risk of internalizing symptoms and perhaps internalizing disorders in adolescent girls.

Abstract

Recent reviews of studies concerning panic attacks in adolescents have emphasized research limitations, noting problems of validity, reliability, and lack of normative data. To address some of these limitations we evaluated two methods of panic ascertainment (questionnaire versus interview), reliability of interview-determined panic, and clinical correlates of panic symptoms in a large sample (N = 1013) of early adolescent girls. The 5.4% of the sample who, when interviewed, reported ever experiencing a panic attack scored significantly higher on measures of depression, anxiety sensitivity, and alcohol use, but were not more avoidant than others. Using the interview as the standard, the questionnaire had a specificity of 81% and a sensitivity of 72%. Adolescents do experience panic attacks-whether identified by questionnaire or interview-although for many the attacks may not be salient. Longitudinal studies are required to determine those qualities of nonclinical panic (severity, context, interpretation/attribution), which render some episodes as clinically meaningful.

Abstract

Risk-factor research refers to the study of antecedent conditions and subsequent outcomes and the ways in which these are interrelated. The research encompasses a broad range of questions and research strategies. The paper discusses the characteristics and contributions of risk-factor research in the context of developmental psychopathology. The ways in which causal paths are conceptualized, the capacity to integrate multiple influences, and applications that can be derived from the findings are discussed. The progression of research is illustrated in relation to key concepts (correlate, risk factor, marker, causal risk factor) that reflect varied levels of understanding antecedent-outcome relations. The identification of causal relations, progressions, and paths over the course of development and the interplay of theory, research, and application are illustrated and discussed.

Abstract

The authors examined factors prospectively associated with age of onset of partial syndrome eating disorders over a 4-year interval in a community sample (N = 877) of high school-age adolescent girls. Four percent developed a partial syndrome eating disorder over the interval. A measure of weight concerns was significantly associated with onset in a multivariate Cox proportional hazard analysis (p < .001). Girls scoring in the highest quartile on the measure of weight concerns had the highest incidence (10%) of partial syndrome onset, whereas none of the girls in the lowest quartile developed eating disorder symptoms. This finding is consistent with both theoretical and clinical perspectives and may represent a useful step toward the establishment of a rational basis for the choice of a prevention intervention target.

Abstract

Signal detection methods were used to develop an algorithm useful in distinguishing those at risk for late relapse from those likely to maintain abstinence. Four subgroups with 24-month survival (nonrelapse) rates ranging from 79% to 33% were identified. Among participants whose depression symptoms decreased from baseline to the end of treatment, lower levels of nicotine dependence were associated with less relapse at the 24-month follow-up (odds ratio = 2.77; 95% confidence interval: 1.36-5.62). Among participants whose depression symptoms increased from baseline to the end of treatment, greater weight gain was associated with less relapse at follow-up (odds ratio = 2.90; 95% confidence interval: 1.41-5.96). This study suggested that it may become possible to use both baseline and treatment information to "titrate" interventions.

Abstract

This paper considers an index to assess the success of blinding with application to a clinical trial of disulfiram. The index increases as the success of blinding increases, accounts for uncertain responses, and is scaled to an interval of 0.0 to 1.0, 0.0 being complete lack of blinding and 1.0 being complete blinding.

Abstract

Associations between affective disorders, anxiety disorders, and substance use disorders were examined in epidemiological studies conducted in Germany, Switzerland, Puerto Rico, and the mainland US. There was a remarkable degree of similarity across studies in the magnitude and type of specific disorders associated with the affective disorders. Comorbidity with affective disorders was greater for the anxiety disorders than for substance misuse. Panic disorder was the subtype of anxiety that was most highly comorbid with depression. Social phobia was the specific phobic type with the strongest association with the affective disorders. The magnitude of associations between substance misuse and affective disorders generally was quite low and less consistent across sites. No major differences were found in the patterns of comorbidity by gender or age group, affective subtype or prevalence period. The onset of anxiety disorders generally preceded that of depression, whereas alcohol misuse was equally likely to pre-or post-date the onset of affective disorders. Finally, comorbidity was associated with an elevation in treatment rates across all sites, confirming Berkson's paradox on an international level.

Abstract

The authors' goal was to determine if the actual treatment of schizoaffective and bipolar affective disorders had changed in light of recent clinical drug trials that have suggested that valproate and carbamazepine may be equivalent in efficacy to lithium.Medication utilization rates for each 6-month period from July 1, 1989, to June 30, 1994, were compiled from the clinical database of the Palo Alto Veterans Affairs Medical Center. Results: The use of valproate and valproate plus lithium was negligible in 1989. by 1994, these medication regimens accounted for 25% of the standard antimanic treatments used for bipolar affective disorder and 38% of the treatments used for schizoaffective disorder. Regimens of carbamazepine and carbamazepine plus lithium dropped from 24% of antimanic treatments in 1989 to 18% in 1994. From 1989 to 1994, there was a decline in the rate of lithium monotherapy for treatment of bipolar affective disorder (from 84% to 43%) and schizoaffective disorder (from 100% to 53%).In the past 5 years, valproate monotherapy has increased as a percentage of total antimanic pharmacotherapies, while lithium monotherapy has declined.

Abstract

DATA ARE PRESENTED for 933 Hispanic and 7087 white men and women, ages 25 to 74, who participated in biennial cross-sectional surveys in California from 1979 to 1990. Using an unadjusted analysis, white women and men had significantly higher mean systolic blood pressures (123.4 mmHg versus 119.6 mmHg) and higher levels of hypertension (29.0% versus 22.9%) than Hispanic women and men (P values greater than 0.001). To reduce bias from confounding, a subset of 702 Hispanics were matched to 702 whites on age, gender, education, city of residence, and time of survey. All ethnic differences in blood pressure became nonsignificant in this analysis. The mean systolic blood pressure for whites was 120.0 mmHg; for Hispanics, 120.7 mmHg (24.4% hypertension for both groups, P values greater than 0.10). These findings show the importance of taking sociodemographic factors into account when examining ethnic differences in blood pressure.

Abstract

A scale for assessing war-zone-related posttraumatic stress disorder (WZ-PTSD scale) was derived from the Symptom Checklist-90-R by identifying items that best discriminated Vietnam theater veterans with and without PTSD (N = 202). The 25-item WZ-PTSD scale had excellent internal consistency, and signal detection analyses revealed that its diagnostic utility was comparable to or exceeded that of several established PTSD scales and measures of global distress. In a cross-validation sample (N = 99), the diagnostic utility of the WZ-PTSD scale was stable, whereas other PTSD scales performed more poorly. The WZ-PTSD scale appears to be a valuable new measure of PTSD that can be particularly useful in archival data sets or in any situation where other PTSD measures are not available.

Abstract

The objective of this study was to examine whether oils high in monounsaturated or polyunsaturated fats have a differential effect on serum lipid levels, using a meta-analytical approach. Fourteen studies (1983 through 1994) were identified that met six inclusion criteria, the primary criterion being that a study have at least two intervention diets that varied in monounsaturated and polyunsaturated fat content but were otherwise similar in total fat, saturated fat, fiber, and dietary cholesterol. Seven studies included a comparable high-saturated fat diet. Standardized effect sizes observed treatment difference in mean end-point lipid levels, divided by the pooled (SD) were calculated for individual studies, then individual effect sizes were pooled. The results indicated no significant differences in total, LDL, or HDL cholesterol levels when oils high in monounsaturated or polyunsaturated fats were compared directly. Triglyceride levels were modestly but consistently lower on the diets high in polyunsaturated fats (P = .05). Replacement of saturated fat with either monounsaturated or polyunsaturated fat led to significant decreases in total and LDL cholesterol (P < .001), and the pooled effect sizes were comparable for either type of unsaturate (effect sizes ranged from -0.64 to -0.68, ie, roughly a decrease of 0.65 mmol/L [25 mg/dL] relative to the high-saturated fat diets). Neither type of unsaturated fat significantly changed HDL cholesterol or triglyceride levels relative to the high-saturated fat diets. In conclusion, the evidence from this meta-analysis strongly indicates there is no significant difference in LDL or HDL cholesterol levels when oils high in either monounsaturated or polyunsaturated fats are exchanged in the diet. Any dietary recommendations for the use of one in preference to the other should be based on outcomes other than serum cholesterol levels.

Abstract

We conducted an exploratory post hoc study that compared the cost effectiveness of five treatments for bulimia nervosa: 15 weeks of cognitive behavioral therapy (CB) followed by three monthly sessions, 16 weeks (Med16) and 24 weeks (Med24) of desipramine (< or = 300 mg/day), and CB combined with desipramine for those durations (Combo16 and Combo24). We illustrate how a treatment's cost effectiveness varies according to when evaluation is done and how effectiveness and cost are defined. At 32 weeks, Med16 appears the most cost-effective treatment, and Combo16 appears the least. At 1 year, Med24 appears the most cost-effective treatment, and Combo16 appears the least. Using this post hoc analysis as an example, we discuss the pitfalls and limitations of cost-effectiveness analysis of psychiatric treatments.

Abstract

The multiple sleep latency test (MSLT) is commonly used as an objective measure of sleepiness. We retrospectively correlated MSLT scores from 147 patients with other information relating to sleepiness, namely demographic information, data from nocturnal polysomnograms (PSGs), and subjective assessments. The only variable that showed a valid and statistically significant correlation with the MSLT score was sleep latency on the PSG. The results were largely similar within subgroups focusing on (1) individuals with the ability to fall asleep on every nap, (2) subjects with abnormally short MSLT scores, (3) nap attempts that were successful, and (4) patients with particular diagnoses. We conclude that the mean sleep latency on the MSLT, in a clinical population, does not correlate well with a number of variables expected to influence sleepiness. While the validated utility of the MSLT in separating patients from normals or in identifying narcolepsy is not disputed, the accuracy of the MSLT as a measure of sleepiness appears to be limited.

Abstract

Although past studies have compared cigarette smoking patterns in Hispanics and whites, few have examined differences within sex and educational subgroups. Data are presented for 1,088 Hispanic women and men (89% Mexican-American origin) and pairwise matched white women and men (544 pairs), aged 25-74 years, who participated in population-based cross-sectional surveys in California in 1979-1990. Each pair was matched on age, sex, educational level, city of residence, and survey time period. There were large differences in smoking prevalence rates between Hispanic and white pairs with low educational attainment. White women and men with less than a high school education were approximately twice as likely to be current daily cigarette smokers as were similarly educated Hispanic women and men (46.1 vs. 20.6% for women and 52.7 vs. 30.1% for men). As the level of education increased, these ethnic differences in smoking decreased and became negligible among those who completed college. Virtually all low-educated white men (92.5%) and most low-educated white women (73.1%) were either current or former daily smokers. There were large ethnic differences in rates of smoking cessation advice from a physician; only 8.3% of low-educated Hispanic men who were current daily smokers had ever been advised by a physician to stop smoking, compared with 59.6% of low-educated white men. These data confirm ethnic differences in smoking behavior and identify the high smoking rates of white men and women with low educational attainment, thus delineating an often unrecognized group toward whom tobacco prevention and cessation activities should be directed.

Abstract

I define three separate and distinct types of non-random comorbidity: epidemiologic, clinical and familial. These might exist singly or in any combination for a pair of disorders. The focus is on their definition and the measurement and interpretation of the types of comorbidity of most common concern: epidemiologic comorbidity. I discuss certain sources of epidemiologic comorbidity such as shared risk factors, or diagnostic 'fuzziness', and I indicate the directions of research design and analyses to disclose such sources.

Abstract

For determination of the effects of weight variability on cardiovascular risk factors, a random community sample of 269 men and 361 women aged 25-74 years, drawn from the Stanford Five-City Project, was followed for up to 10 years (1979-1989). Systolic and diastolic blood pressure, total and high density lipoprotein cholesterol, and pulse were measured. Body mass index slope (BMI-slope) was determined by regressing five BMI values on time for each individual. BMI variability was defined as the root mean square error (BMI-RMSE) of a regression line fitted to each individual's BMI values over time. The slopes of the five cardiovascular risk factors were most strongly related to the baseline value of each risk factor and BMI-slope in both men and women. Neither BMI-RMSE nor the interaction of BMI-RMSE with BMI-slope was related to risk factor slopes. In this population, BMI variability had little impact on cardiovascular risk factors compared with BMI-slope and baseline BMI.

Abstract

The objective of this study was to determine the effects of age and life-style factors on body mass index (BMI) in a longitudinal, community-based sample. A total of 568 men and 668 women (20-60 years of age) were randomly chosen from four Northern California communities and followed for up to 7 years. Age, sex, marital status, smoking status, hours of television watched, frequency of consumption of several food items, and physical activity were used to predict rate of change of body mass index (BMI-slope). BMI increased the most for both sexes through at least age 54. The BMI-slope was higher for women compared with men, and for smokers who stopped compared with those who never smoked or continued to smoke during the study. The BMI-slopes were lower for individuals who increased activity. Other life-style variables had weak or inconsistent effects on the BMI-slope. We conclude that the BMI-slope increases over age for both sexes and that increased physical activity may reduce the BMI-slope.

Abstract

Community-based prospective studies are needed to shed light on mechanisms that may influence development of eating disorders and identify variables that could serve as potential targets for prevention efforts. In this paper we examine level of weight preoccupation and other variables prospectively associated with age of onset of eating disorder symptoms over a 3-year interval in a community sample (N = 939) of young adolescent girls. 3.6% (32/887) experienced onset of symptoms over the interval. Only one factor, a measure of Weight Concerns, was significantly associated with onset (p < .001). Girls scoring in the highest quartile on the measure of Weight Concerns had the shortest survival time (12% incidence by age 14.5) and those scoring in the lowest quartile had the highest survival time (2% incidence by age 14.5; p < .001). This finding is consistent with both theoretical and clinical perspectives and represents one of the first prospective demonstrations of a linkage between weight and body shape concerns and later onset of eating disorder symptoms. An understanding of the independent variables that predispose girls to development of symptoms is a useful step towards the establishment of a rational basis for the choice of a prevention intervention target.

Abstract

Approximately 2%-5% of autistic children show cytogenetic evidence of the fragile X syndrome. This report tests whether infantile autism in multiplex autism families arises from an unusual manifestion of the fragile X syndrome. This could arise either by expansion of the (CGG)n trinucleotide repeat in FMR-1 or from a mutation elsewhere in the gene. We studied 35 families that met stringent criteria for multiplex autism. Amplification of the trinucleotide repeat and analysis of methylation status were performed in 79 autistic children and in 31 of their unaffected siblings, by Southern blot analysis. No examples of amplified repeats were seen in the autistic or control children or in their parents or grandparents. We next examined the hypothesis that there was a mutation elsewhere in the FMR-1 gene, by linkage analysis in 32 of these families. We tested four different dominant models and a recessive model. Linkage to FMR-1 could be excluded (lod score between -24 and -62) in all models by using probes DXS548, FRAXAC1, and FRAXAC2 and the CGG repeat itself. Tests for heterogeneity in this sample were negative, and the occurrence of positive lod scores in this data set could be attributed to chance. Analysis of the data by the affected-sib method also did not show evidence for linkage of any marker to autism. These results enable us to reject the hypothesis that multiplex autism arises from expansion of the (CGG)n trinucleotide repeat in FMR-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

To test the hypothesis that the patterns of pubertal progression, early vs late puberty and fast vs slow, are associated with the age at which girls start to drink alcohol and smoke cigarettes.The study included 1463 female students, 10.7 to 18.2 years of age, who were assessed five times during the 2.7-year study. Data regarding pubertal stage, alcohol use, and cigarette use were obtained at each assessment. These data were used to calculate two indexes of pubertal development, the age at which the midpoint of puberty was achieved and the rate of progression through puberty, and the ages when each subject first drank, first drank moderate amounts of alcohol, and first smoked.Girls with earlier puberty (midpoint < 12.2 years) first reported drinking any alcohol at a median age of 12.5 years, 0.7 years younger than girls whose puberty was later. Similarly, girls with earlier puberty reported drinking moderate amounts of alcohol at a median age of 13.7 years, 0.9 years younger than girls with later puberty. Girls with earlier puberty further reported first smoking cigarettes at a median age of 12.8 years, 0.6 years younger than girls with later puberty. The rate of pubertal progression was significantly associated only with the age when girls first drank moderate amounts of alcohol.Earlier puberty is associated with a younger age of onset for both drinking and smoking among adolescent girls.

Abstract

This field trial was designed to answer four questions. First, are patients presenting with anxious or depressed symptoms that are associated with significant impairment but do not meet DSM-III-R definitional thresholds for axis I anxiety or mood disorders? Second, is the impairment experienced by these patients simply the consequence of the severity of their medical conditions? Third, what percent of these patients present with depressive symptoms only, anxious symptoms only, and a mixture of both? Fourth, how should the operational criteria for the syndrome(s) presented by these patients be defined?A total of 666 patients from five primary care medical sites and two outpatient mental health sites were administered a semistructured psychiatric interview.Patients presenting with affective symptoms that did not meet definitional thresholds for DSM-III-R axis I disorders were at least as common as patients with several of the already established anxiety and mood disorders in each of the seven sites, and their disorders were associated with significant distress or impairment. A nonspecific pattern of anxious and depressed symptoms was the modal presentation among these patients with currently subdefinitional threshold disorders, and they could be significantly differentiated in terms of current symptoms from patients presenting with a principal diagnosis of generalized anxiety disorder, major depressive episode, or panic disorder with agoraphobia.The authors recommend that a mixed anxiety-depression category be included in the DSM-IV appendix for proposed diagnostic categories that need further study. A criteria set is proposed.

Abstract

This paper presents a prospective examination of sociodemographic, psychosocial, and physiologic characteristics associated with positive change in cardiovascular disease risk factors during a 6-year multiple risk factor intervention study.Data are presented on 221 women and 190 men (aged 25 through 74 years) who participated in four cohort surveys (1979 through 1985). A signal detection model was used to identify baseline variables that best divide the sample into subgroups on the basis of the probability of positive change in a composite risk factor score.Sixty-nine percent of the respondents showed a positive change in risk factor score during the intervention. The subgroup with the highest proportion of positive changers (83%) was composed of older adults (> 55 years) with the highest perceived risk, highest health media use, and highest blood pressure and cholesterol levels. The subgroup with the lowest proportion of positive changers (42%) was the least educated, was the most likely to be Hispanic, and had the lowest health knowledge and self-efficacy scores.The differing composition of subgroups who respond or do not respond to community cardiovascular disease interventions illustrates the need to develop specific interventions that target different age, socioeconomic, and cultural subgroups.

Abstract

Twenty-seven narcoleptic patients severely affected with cataplexy completed four symptom diaries over a 4-month period in order to clarify some of the controversies surrounding assessment of anticataplectic medications. The home diary method was found to be a viable model for the assessment of anticataplectic activity. Assessment of reliability in 1-, 2-, 3-, 4-, 5- and 10-day intervals indicated that reliability increases with the number of days included. A 10-day design was found to be optimal. Reliability decreased, however, with each successive diary over the 4-month period. Power analysis indicates that two groups of 30-40 subjects in a parallel design, or one group of 30-40 subjects in a crossover design, would be sufficient to demonstrate a significant therapeutic anticataplectic effect in most cases. A "first diary effect" was observed, suggesting that a training period prior to the actual trial might improve reliability. Whether the patient was treated or untreated with stimulant medications did not affect severity or fluctuation of cataplexy, suggesting that both groups of patients could be included in therapeutic trials. No time-of-day fluctuation was observed in the daily distribution of cataplexy attacks. Sudden increases in cataplexy were often, although not always, caused by unusual emotional events or sleepiness. The finding of a long-lasting "precataplectic" feeling or "aura" pointed to the need to carefully clarify the symptom prior to beginning a therapeutic trial.

Abstract

The goal of this study is to propose conceptual and operational definitions of "state" and "trait", and a methodological approach to document empirically the state and trait aspects of a characteristic. An example using real data related to rapid eye movement latency for patients with major depressive disorder is presented to model the application of this method.

Abstract

Evidence from twin and family studies strongly suggests that genetic factors play a prominent role in the etiology of some cases of infantile autism. Genetic factors would be expected to be especially strong in families with multiple autistic members (multiplex families). This report describes the identification and evaluation of 44 families with two or more autistic children collected as part of a genetic linkage study in autism. Families were referred with a presumptive classification of multiplex autism. Children referred as autistic, as well as their presumptively normal siblings, were assessed using the Autism Diagnostic Interview (ADI) and the Autism Diagnostic Observation Scale (ADOS). Thirty-seven of the 44 families (87%) had at least two children who met diagnostic criteria for autism on the ADI. Of the total group of 117 children evaluated in those families, 83 (71%) met all ADI criteria and could be unambiguously classified as autistic (affected), 26 (22%) met none of the ADI criteria and were classified as not autistic (unaffected), and 8 (7%) were classified as uncertain because they met one or more but not all of the ADI cutpoints. Autistic siblings were not significantly concordant for most autism characteristics, for IQ, or for verbal ability. Significant concordances were found, however, for behaviors related to rituals and repetitive play, and for social impairments in the expression and understanding of facial expressions of emotion.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

To expand on a recent study of 42 patients with probable Alzheimer's Disease that found that the only significant predictors of certain clinical end points were the degree of severity features at entry ("how far").A case series study of a cohort of 81 patients with Alzheimer's disease that used survival analysis methods similar those of the previous study but included a new technique for calculating rate of progression ("how fast") as well as entry characteristics ("how far").A university medical center and its affiliated Veterans Affairs Medical Center.All patients with probable and definite Alzheimer's disease studied at the Aging Clinical Research Center at Stanford University, Palo Alto, Calif, in the years 1981 and 1992 who met the following criteria: a mild to moderate level of severity of the disease (Mini-Mental State Examination score of 15 or above) at entry into the study and a minimum of three test points spaced approximately 6 months apart (to allow estimation of rate of progression). A total of 81 such patients were identified. These patients had been followed up for a mean of 4.53 +/- 2.3 years, with a range of 1.0 to 14.5 years.The outcome measure was the average rate of decline on the Mini-Mental State Examination.The results of our study replicated a previous finding that the degree of severity is a strong predictor of time course, but in addition we found that the rate of progression also appears to be a strong predictor of clinical course.There appears to be substantial heterogeneity in the rate of progression in patients with Alzheimer's disease, and, like initial degree of severity, rate of progression appears to be a strong predictor of clinical course.

Abstract

To present a new model for analyzing longitudinal data. The trilinear model is superior to the commonly used linear model that includes the flawed assumption that decline is uniform throughout the course of disease--an assumption that does not correspond to clinical observations.A longitudinal cohort sample was used to compare the linear and trilinear models. Simulated longitudinal data were generated to assess classification errors with the trilinear model.The subjects were 80 patients with Alzheimer's disease tested in a hospital out-patient clinic.The trilinear model describes Alzheimer's disease as proceeding through three periods: An initial period of stability before detectable decline, a period of decline, and a final period of stability during which there is no further detectable decline. A program for the Apple Macintosh computer is available at no charge to apply the model to data.The analyses indicated that the trilinear model provides a better reflection of decline in Alzheimer's disease than does the linear model. This advantage is present whether the periods of stability reflect a "true" lack of decline or insensitivity of a measurement instrument.The trilinear model provides not only a more accurate estimate of the average rate of change, but also (when possible) estimates of the point at which decline begins and ends. Also, more detailed comparisons of tests could be made by using the trilinear parameters. The trilinear model would benefit researchers engaged in longitudinal research of progressive disorders.

Abstract

This is the first long-term, controlled study evaluating the effectiveness of a prevention curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls. Nine hundred sixty-seven sixth and seventh-grade girls were randomized to experimental healthy weight regulation curriculum or no-treatment control classes. A prevention intervention was developed around three principal components: (1) Instruction on the harmful effects of unhealthful weight regulation; (2) promotion of healthful weight regulation through the practice of sound nutrition and dietary principles and regular aerobic physical activity; (3) development of coping skills for resisting the diverse sociocultural influences that appear linked to the current popular obsessions with thinness and dieting. The intervention failed to achieve the hoped-for impact. We did observe a significant increase in knowledge among girls receiving the intervention and among high-risk students only, there was a small albeit statistically significant effect on body mass index. These findings question the wisdom of providing a curriculum directed at all young adolescents, most of whom are not at risk to develop an eating disorder. Rather than targeting the entire population, a healthy weight curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls might better focus on "at risk" students.

Abstract

A new neonatal medical index (NMI) was used to predict the mental and motor development of low birth weight, preterm infants up to 3-years-old. The NMI is a summary score of only a few clinically salient items that are readily available on brief chart review. The sample consisted of 512 of 608 infants randomly assigned to the control group of the eight-site Infant Health and Development Program and on whom the complete set of developmental outcome measures was available. The developmental tests administered were the Bayley Scales at 12 and 24 months and the Stanford-Binet at 3 years. The findings indicated the NMI was predictive of later cognitive and motor development, and in infants born weighing less than 1500 g, the effects of neonatal medical complications continued to adversely influence these children's development to at least 3 years of age. In the heavier babies the developmental effects of sociodemographic factors predominated by 24 months and beyond.

Abstract

To examine the relationships between hours of television viewing and adiposity and physical activity among female adolescents, a cohort study with follow-up assessments 7, 14, and 24 months after baseline was conducted. All sixth- and seventh-grade girls (N = 971) attending four northern California middle schools were eligible to participate. Six hundred seventy-one students had sufficient data for baseline cross-sectional analyses, and 279 students in a no-intervention cohort had sufficient data for longitudinal analyses. The baseline sample had a mean age of 12.4 years and was 43% white, 22% Asian, 21% Latino, 6% Pacific Islander, 4% black, 2% American Indian, and 2% other. Hours of after-school television viewing, level of physical activity, and stage of sexual maturation were assessed with self-report instruments. Height, weight, and triceps skinfold thickness were measured and body mass index (ratio of weight [in kilograms] to height [in meters] squared) and triceps skinfold thickness were adjusted by level of sexual maturity for the analyses. Baseline hours of after-school television viewing was not significantly associated with either baseline or longitudinal change in body mass index or triceps skinfold thickness. Baseline hours of after-school television viewing was weakly negatively associated with level of physical activity in cross-sectional analyses but not significantly associated with change in level of physical activity over time. All results were essentially unchanged when adjusted for age, race, parent education, and parent fatness. Among adolescent girls, television viewing time appears to have only weak, if any, meaningful associations with adiposity, physical activity, or change in either over time.

Abstract

Mothers, teachers, and assistant teachers completed the Richman Behavior Checklist (BCL) at ages 2 and 3 years and the Achenbach Child Behavior Checklist for Ages 2-3 (CBCL 2-3) at 3 years for a large sample of low birth weight, premature children. Interinstrument correlations for total scores were moderate, higher for teachers and assistant teachers than for mothers, with moderate temporal stability for BCL scores. Interrater agreement for either total scores or classifications of clinically significant scores was moderately high between teachers and assistant teachers only, and children identified as disturbed by mothers versus teachers represent almost nonoverlapping groups. Furthermore, many more children were identified as disturbed using the BCL. The most powerful predictors of mothers' total CBCL 2-3 scores were HOME Inventory scores and self-reported depression. The use of these scales in clinical and research contexts is discussed.

REPORTING THE SIZE OF EFFECTS IN RESEARCH STUDIES TO FACILITATE ASSESSMENT OF PRACTICAL OR CLINICAL-SIGNIFICANCEPSYCHONEUROENDOCRINOLOGYKraemer, H. C.1992; 17 (6): 527-536

Abstract

"Statistically significant" results may lack practical or clinical significance, and the description of results in reports of research studies is frequently incomplete or misleading in presentation of data necessary to assess such significance (effect sizes). Various common presentations are discussed, and one method of presentation of results is proposed that not only encompasses all the others, but enhances the scope of useful information conveyed in a research report. The results of the Infant Health and Development Program (IHDP) are used to illustrate the method.

Abstract

Results of a prospective examination (N = 618) of factors associated with smoking relapse are reported. At 1-year follow-up, a modified version of the Fagerstrom Tolerance Questionnaire (Dependence Index; DI) and a measure of craving entered the logistic model (odds ratio of 2.7 [p less than .001]). At Year 2, only the DI entered the model (odds ratio of 2.2 [p less than .001]). The ability of signal detection analysis (SDA) to produce clinically useful decision rules was also examined. At Year 1, SDA produced 1 subgroup with a 25% nonrelapse rate and another with a 9% nonrelapse rate (odds ratio of 3.4 [p less than .001]). At Year 2, SDA produced 1 subgroup with a nonrelapse rate of 19% and another with a nonrelapse rate of 7% (odds ratio of 3.0 [p less than .001]). The use of signal detection methods may help clinicians to identify those at greater or lesser risk of relapse.

Abstract

To evaluate the effectiveness of practice guidelines for return to work after acute myocardial infarction when disseminated from a university-based setting to a practice-based setting.Randomized clinical trial.A total of 187 patients with uncomplicated acute myocardial infarction.Patients were randomly assigned to the intervention (n = 95) or to usual care (n = 92). The intervention consisted of a treadmill test, a counseling session based on the test results, and a consultation letter from a cardiologist to the primary care physician. Individualized recommendations for the timing of return to work, contained in the consultation letter, were based on the patient's risk for recurrent cardiac events.Questionnaire, chart review, and a phone interview documented the timing of return to work and the rates of cardiac death, coronary angioplasty, coronary artery surgery, and recurrent myocardial infarction.Median intervals between acute myocardial infarction and return to work were similar in both groups (intervention, 54 days; usual care, 67 days; P greater than 0.2). Among patients without myocardial ischemia, however, the interval was shorter in the intervention group than in the usual care group (38 days compared with 65 days, respectively, P = 0.008). Among patients with myocardial ischemia, intervals were similar in both groups (80 days compared with 76 days, respectively, P greater than 0.2).Practice guidelines developed in a university-based setting were not as successful in hastening return to work after uncomplicated acute myocardial infarction when tested in a practice-based setting. Physicians' reluctance to follow guidelines for patients with myocardial ischemia reflected their concern with prognosis even though medical outcome was good.

Abstract

The Infant Health and Development Program is a national collaborative study to test the efficacy of combining early child development and family support services with pediatric follow-up to reduce the incidence of health and developmental problems among low birth weight, preterm infants in eight medical school sites. Its efficacy in enhancing intellectual outcomes at age 3 in more and less environmentally vulnerable, low birth weight, preterm children, as defined by maternal education (high school completion or less vs some college) and race (black vs white/other), is explored. Children whose mothers had a high school education or less benefited from the intervention. This was true for both the black and white samples. Children whose mothers had attended college did not exhibit significant enhancement in IQ scores at 3 years. Birth weight affected the response to treatment for one of the four subgroups: Among white mothers with some college, the lighter (less than 2000 g) low birth weight, preterm children were less influenced by the intervention than were the corresponding heavier children. Implications for targeting certain subgroups of low birth weight, preterm children for services are considered.

Abstract

The ongoing experience of panic disorder was assessed in 20 female subjects, to determine psychological precursors to panic attacks. Measures of anxiety, threat, control, prediction of panic, and symptoms were assessed at hourly intervals during waking hours for one week. Measures were taken using a portable computerised diary which prompted for and stored responses. Patients' ratings of the prediction of panic attacks were the only significant precursors to panic attacks. This supports recent research that expectancy is important in panic onset. The data also suggested that anxiety levels follow a circadian pattern.

Abstract

When faced with a decision whether or not to treat a patient, to enter or to withdraw a patient from a clinical trial, or any other such binary decision, based on diagnosis with unsatisfactory reliability, can a consensus diagnosis be used to improve reliability? If so, exactly how? That is the question I address here. I draw comparisons and contrasts between the known results with an interval consensus and those with a binary consensus and suggest tactics for use in a pilot study to answer the above questions.

Abstract

The problem of measuring reliability of categorical measurements, particularly diagnostic categorizations, is addressed. The approach is based on classical measurement theory and requires interpretability of the reliability coefficients in terms of loss of precision in estimation or power in statistical tests. A general model is proposed, leading to definition of reliability indices. Design and estimation approaches are discussed. Issues and approaches found in the research literature that either lead to confusing or misleading results are presented. The signs and symptoms of unreliable diagnoses are identified, and strategies for improving the reliability of such diagnoses are discussed.

Abstract

To obtain follow-up growth data on a large sample of low birth weight, preterm infants, 985 infants were monitored longitudinally in an eight-site collaborative program until 3 years of age, corrected for prematurity. The growth of 608 of these infants was described previously through 1 year of age. In the full sample, 149 infants weighed less than or equal to 1250 gm at birth, 474 between 1250 and 2000 gm, and 362 between 2000 and 2500 gm. Thirty-three percent were white, 53% were black, and 11% were Hispanic. Weight, length, and head circumference were measured at birth and at 40 weeks and 4, 8, 12, 18, 24, 30, and 36 months gestation-corrected age in at least 862 infants each time. Descriptive statistics and estimated growth rates for all growth variables and a body mass index (height in kilograms per square meter), plotted by sex and birth weight group, demonstrated growth patterns lower than published standards for term infants of the same age and sex. These patterns of growth differed by birth weight group. Little catch-up was noted by the 36-month examination for gestation-corrected age for any birth weight group. We conclude that low birth weight, preterm infants have different patterns of growth than term infants during the first 3 years of life, even with plotting corrected for gestational age.

Abstract

--To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy, sedentary older adults.--Year-long randomized, controlled trial comparing (1) higher-intensity group-based exercise training; (2) higher-intensity home-based exercise training; (3) lower-intensity home-based exercise training; or (4) assessment-only control.--General community located in northern California.--One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease. One out of nine persons contacted through a community random-digit-dial telephone survey and citywide promotion were randomized.--For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise training, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate.--Treadmill exercise test performance, exercise participation rates, and heart disease risk factors.--Compared with controls, subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months (P less than .03). Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training. Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition (P less than .0005). There were no significant training-induced changes in lipid levels, weight, or blood pressure.--We conclude that (1) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary, healthy older adults; (2) home-based exercise was as effective as group exercise in producing these changes; (3) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting; and (4) the exercise programs were relatively safe.

Abstract

Weight-for-height indexes are often used in the clinical assessment of obesity in children and adolescents. The direct measurement of adiposity, using hydrostatic weighing and other techniques, is not feasible in studies involving young children or with large numbers of older subjects. Ratios of weight relative to height, such as the body-mass index (weight/height), may be used as indirect measures of obesity and correlate with more direct measures of adiposity. Using data from the First National Health and Nutrition Examination Study, 1971 to 1974, standardized percentile curves of body-mass index for white children and adolescents were developed. These curves may be used to monitor the body-mass index of white children and adolescents longitudinally and for comparing an individual with others of the same sex and age.

TO INCREASE POWER IN RANDOMIZED CLINICAL-TRIALS WITHOUT INCREASING SAMPLE-SIZEKraemer, H. C.US GOVERNMENT PRINTING OFFICE.1991: 217-224

Abstract

The power of a randomized clinical trial (RCT) depends on two factors: sample size and effect size. Most psychiatric research design strategies focus on increasing sample size, despite major problems in recruiting large numbers of subjects or funding such costly studies. It is possible to increase power in RCTs in a variety of ways without increasing sample size, in essence by increasing effect size by decreasing within-group variance. Such strategies are presented and discussed.

Abstract

Theories linking anger and blood pressure (BP) reactivity to cardiovascular disease must be able to identify naturally occurring stressors that arouse emotion with sufficient frequency to cause chronic physiologic stress. We examine the impact of normal family arguments on 43 patients (24 women, 19 men) with essential hypertension. Patients and their partners discussed a threatening disagreement for 10 min while BP and conversation were recorded. Discussing problems increased BP, but the causal pathways differed by sex. In women, hostile interaction and marital dissatisfaction were associated with increased BP; "supportive" or "neutral" exchanges were unrelated to BP. In men, BP fluctuations were related only to the patient's speech rate. These findings are consistent with other research on sex differences in communication and social problem-solving styles and implicate different mechanisms (frequent anger, active coping) through which marital discord could increase risk. Implications for intervention are considered.

Abstract

The second annual MacArthur Foundation Network I Methodology Workshop focused on the different approaches to implementing randomized controlled clinical trials (RCTs) and the situations in which each approach seems to be most appropriate. We reviewed the advantages and disadvantages of various approaches (single-site RCTs, multisite collaborative RCTs, multiple single-site RCTs, and meta-analysis of existing RCTs), and we make recommendations based on these considerations proposed.

Abstract

The Mini-Mental State Examination (MMSE) is a commonly used instrument for assessing mental impairment. Previous proposals for its underlying structure have focused on scores obtained from a single administration of the test. Because the MMSE is widely used in longitudinal studies, we examined the pattern of relations among the rates of chance of the items. Data were obtained from 63 subjects for 1.5 years or more. The relations among the rates of change of the MMSE items were described by a five-factor solution that accounted for 75% of the variance and comprised factors pertaining to orientation and concentration, obeying commands, learning and repetition, language, and recall. This was in contrast to the structure of the scores obtained from a single administration of the MMSE, which was best described by a two-factor solution. In order to provide a clinical validation, factor scores derived from the MMSE factors were used to predict scores on the Memory and Behavior Problems Checklist and the Brief Cognitive Rating Scale.

Abstract

To obtain growth data on a large sample of low birth weight preterm infants, we monitored 608 infants longitudinally in an eight-site collaborative program. Ninety-nine infants weighed less than or equal to 1250 gm at birth, 289 between 1250 and 2000 gm, and 220 infants between 2000 and 2500 gm. Thirty-four percent were white, 52% black, and 14% Hispanic. Weight, height, and head circumference were measured at birth and at 40 weeks and 4, 8, and 12 months of gestation-corrected age on at least 553 infants each time. Descriptive statistics for all growth variables and a body mass index (kilograms per square meter), plotted by sex and birth weight group, demonstrated growth patterns lower than published standards for term infants of the same age and sex. These patterns of growth differed by birth weight group. No catch-up growth was noted by the 12-month examination (gestation-corrected age) for any birth weight group. We conclude that low birth weight preterm infants have different patterns of growth than term infants during the first year of life, even with plotting corrected for gestational age.

Abstract

In a previous study we found that a vigorous infant feeding style measured in the laboratory at 2 and 4 weeks of age predicted the degree of adiposity at 1 and 2 years of age. A follow-up of this cohort of infants at 3 and 6 years of age is now reported. Factors predicting adiposity, measured by body mass index at 3 years of age, were pressure of suckling, with high-pressure sucking (denoting a vigorous feeding style) associated with greater adiposity, and time of introduction of solid food, with delayed introduction of solid food or breast-feeding longer than 5 months, or both, being associated with greater adiposity. Predictive factors at 6 years of age were adiposity at birth, with greater adiposity at birth predicting greater fatness at 6 years, parental education, with less education associated with fatness, and a prolonged period of breast-feeding with delayed introduction of solid food. These factors accounted for 40.4% of the variance in adiposity at 3 years of age and 31.2% at 6 years. The effects of social learning on body mass index, indicated by parental educational level, appear to strengthen over time, whereas the effects of the vigorous feeding style wane.

Abstract

The feasibility and cost-effectiveness of estimation of kappa using a case-control method of sampling, proposed by Jannarone, Macera, and Garrison (1987, Biometrics 43, 433-437), is provided support. However, in this article unrealistic assumptions in their presentation are identified and more general results for more realistic settings are provided.

Abstract

Various options available for the randomization of subjects into groups in a clinical trial are discussed, emphasizing the issues of logistics given less focus in more mathematical treatments. We discuss advantages and disadvantages of total randomization, of Zelen-type randomization procedures, of Efron-type procedures vs more classical blocking procedures to control the balance between groups, and of Simon-Pocock-type procedures vs more classical stratification for controlling possible biases in prognostic factors. Finally, we discuss issues related to choice and implementation of randomization procedures. The discussion is illustrated with the processes of decision-making in a national collaborative randomized clinical trial, the Infant Health and Development Program.

Abstract

This study describes an attempt to define intrauterine growth retardation low birth weight preterm infants by comparing reference standards for intrauterine growth in weight, length, and head circumference on their variability across ethnic groups and cities, and on their specificity in independently classifying infants as short, thin, or having small heads. The sample consisted of 985 inborn preterm low birth weight infants enrolled at eight participating sites in a randomized clinical trial using uniform sampling criteria. When gestational age was used as the reference standard, striking differences were found by ethnicity and site in the prevalence of low weight infants at birth. These differences, as well as the potentially false overlap of classification, were attenuated when the use of gestational age as a reference standard was used only for birth length, while length itself was used (as an alternative to gestational age) as the reference standard for birth weight, and weight was used as the reference standard for head circumference. These results raise questions about the use of gestational age as the primary or only reference standard in assessing weight and head circumference at bith.

Abstract

The effect of psychosocial intervention on time of survival of 86 patients with metastatic breast cancer was studied prospectively. The 1 year intervention consisted of weekly supportive group therapy with self-hypnosis for pain. Both the treatment (n = 50) and control groups (n = 36) had routine oncological care. At 10 year follow-up, only 3 of the patients were alive, and death records were obtained for the other 83. Survival from time of randomisation and onset of intervention was a mean 36.6 (SD 37.6) months in the intervention group compared with 18.9 (10.8) months in the control group, a significant difference. Survival plots indicated that divergence in survival began at 20 months after entry, or 8 months after intervention ended.

Abstract

Thorough medical evaluation of 529 patients drawn from eight program categories in California's public mental health system revealed active, important physical disease in 200 patients who had 291 diseases. Fourteen percent of the patients had diseases known to themselves but not to the mental health system, and 12% of the patients had diseases newly detected by the study team. We estimate that of the more than 300,000 patients treated in the California public mental health system in fiscal year 1983 to 1984, 45% had an active, important physical disease. The mental health system had recognized only 47% of study patients' physical diseases, including 32 of 38 diseases causing a mental disorder and 23 of 51 diseases exacerbating a mental disorder. Patients treated in public sector mental health facilities should receive careful medical evaluations.

THE USE OF SIGNAL-DETECTION THEORY TO ASSESS DSM-III-R CRITERIA FOR AUTISTIC DISORDERJOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRYSiegel, B., Vukicevic, J., Elliott, G. R., Kraemer, H. C.1989; 28 (4): 542-548

Abstract

Sixty cases from the DSM-III-R field trials for autistic disorder (AD) were studied to derive an optimally sensitive and specific combination of scoring criteria based on the 16 DSM-III-R criteria for AD. Signal detection theory, a statistical method new to psychiatric research, was applied. Two of the sixteen criteria tested with this methodology yielded a sensitivity of 0.82, a specificity of 0.89, and a total predictive value of 0.91 relative to clinical diagnosis. Excluded criteria were redundant; unrelated to diagnosis; or highly correlated with degree of mental retardation, mental age, and/or chronological age.

Abstract

The economic consequences of an Occupational Work Evaluation designed to identify low risk patients recovering from uncomplicated acute myocardial infarction (AMI) and hasten their return to work was evaluated in a randomized trial. Two hundred one employed, clinically low risk men recovering from AMI were randomized to undergo an intervention (intervention group, 99 patients) consisting of an Occupational Work Evaluation or to receive usual care (usual care group, 102 patients). The time to return to work was reduced from 75 days in usual care patients to 51 days in intervention patients (p less than 0.002). Significant differences were found between groups for medical costs and occupational income during follow-up. Total medical costs per patient were lower in the intervention patients than in the usual care patients in the 6 months after AMI ($2,970 vs $3,472). Occupational income per patient was higher in intervention patients than in the usual care group in the 6 months after AMI ($9,655 vs $7,553). The per capita benefit accounting for medical costs and occupational income was $6,685 for intervention patients and $4,081 for usual care patients. Projected to the greater than 300,000 low risk, employed survivors of AMI annually in this country, the savings generated by the Occupational Work Evaluation could yield an annual economic benefit greater than 800 million dollars.

Abstract

Two general but different contexts in which kappa might be used are defined: agreement and association. Two models, one for agreement and one for utility of association, are defined yielding different kappa coefficients and different sampling theory. Asymptotic results are derived for both models. Small-sample evaluations are presented for the model for agreement.

Abstract

To determine if an occupational work evaluation could shorten the time to return to work, 201 employed men aged 49 +/- 7 years who were recovering from uncomplicated myocardial infarction were randomized to usual care (n = 102) or to an occupational work evaluation (n = 99). The occupational work evaluation consisted of a symptom-limited treadmill test performed 23 +/- 3 days after myocardial infarction and a formal recommendation to the patient and primary physician that the patient return to work within the next two weeks. The groups did not differ in age, medical status, comorbid disease, occupation type, or years on the job. At six months, 92% of patients receiving the intervention and 88% of patients receiving usual care were working either full- or part-time. Return to full-time work occurred at a median of 51 days in patients receiving the intervention and 75 days in patients receiving usual care. This 32% reduction in the convalescence period was associated with +2102 of additional earned salary per intervention patient in the six months after myocardial infarction. One or more recurrent cardiac events occurred in 14 intervention patients (one death, one nonfatal myocardial infarction, three angioplasties, and nine coronary surgeries) and in 13 usual-care patients (two deaths, three nonfatal myocardial infarctions, six angioplasties, and seven coronary surgeries) in the six months after myocardial infarction. The early return to work of low-risk patients based on an occupational work evaluation is associated with important economic benefits.

Abstract

Alcohol is a frequently abused drug among adolescents. In adults, alcohol alters iron metabolism, predisposing to excess hepatic iron storage and, possibly, liver damage. The purpose of this study was to determine whether alcohol is associated with an elevated serum iron concentration and transferrin saturation in adolescents, and to determine the contribution of oral contraceptive use to these abnormalities. Adolescents (591 male and 614 female) aged 16 to 19 years, who participated in the first National Health and Nutrition Examination Survey from 1971 to 1973, were grouped according to their reported frequency of alcohol intake. Drinking frequency was associated with serum iron concentrations in boys and girls, and with total iron-binding capacity, transferrin saturation, and hemoglobin concentration in boys. Alcohol use was associated with an elevated serum iron concentration only in oral contraceptive nonusers. Adolescents who use alcohol have an elevated serum iron concentration, and male alcohol users have an increased transferrin saturation as well. These abnormalities may be precursors of hepatic iron overload and chronic liver damage.

Abstract

While we agree with the general message of the Thompson and Walter paper on the use and value of kappa, the mathematical bases of these conclusions, their equations, tables, and figures are based on mathematical assumptions so limiting that their application to real data is questionable. As a result, several of their specific conclusions are misleading. Some of the same results are here obtained without the limiting restrictions. From these results, the value of kappa as a measure of reliability, validity and (possibly) of general 2 x 2 association is demonstrated.

Abstract

This report discusses many of the issues raised during a two-day institute that focused on methodological problems encountered in psychiatric research. The topics range from the problems with psychiatric diagnosis and measurement to sampling issues and biases to specific statistical concerns. Attention is given to the need for improved communication and collaboration between psychiatric researchers and biostatisticians.

Abstract

Using data from 179 preterm infants, a neurobehavioral maturity assessment was developed by using a process in which clusters characterized by conceptual coherence and face validity were systematically subjected to statistical analyses designed to test whether they also had high test-retest reliability, statistical cohesion, and developmental validity. The psychometric soundness of the test items was made a precondition for their inclusion into the assessment procedure. Also tested were cluster redundancy, as well as the impact of gestational and conceptional age, and of postbirth influences on the functions tested. 8 dimensions of neurobehavioral functioning were found to be stable with a test-retest reliability of at least .6 or higher on 2 consecutive days, nonredundant and developmentally valid. They were: Active Tone/Motor Vigor, Alertness and Orientation, Excitation Proneness, Inhibition Proneness, Scarf Sign, Popliteal Angle, Maturity of Vestibular Response, and Vigor of Crying.

Abstract

Research in exercise training of healthy persons, which has been conducted almost exclusively in supervised group programs, is relatively expensive for the investigator and inconvenient for the participant. To overcome these obstacles, self-monitored moderate-intensity home-based exercise training was prescribed for 28 middle-aged men and 26 middle-aged women. The median energy expenditure prescribed for each of 5 weekly exercise sessions was 4 cal/kg body weight, or 317 kcal for men and 265 kcal for women, corresponding to a median duration of 45 and 60 minutes, respectively. In the next 24 weeks, peak oxygen uptake increased 13.7% in men who exercised, from 31 +/- 4 to 37 +/- 4 ml/kg/min, and 10% in women who exercised, from 26 +/- 4 to 29 +/- 5 ml/kg/min (p less than 0.001 for both comparisons). The proportion of prescribed caloric expenditure per session, which was documented by a solid-state heart rate recorder, was 108% in men and 90% in women. The duration of training at heart rates above the prescribed range approximated 10 minutes per session for both men and women; the proportion of total caloric expenditure represented by exercise at heart rates exceeding the prescribed limit was 9% for men and 4% for women. The proportion of time spent within the prescribed heart rate range during training sessions was 76% for men and 84% for women. Training-induced musculoskeletal problems were reported by 6 men and no women. No subject sought medical attention and all resumed training within 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

The relative validities of three clinical assessment methods for estimating gestational age in newborn low birth weight infants were evaluated with reference to estimates based on the date of the mother's last menstrual period. For 1246 infants in eight diverse institutions, estimates based on physical criteria correlated more strongly with dates estimates, yielded estimates more similar on average to dates estimates, and yielded higher proportions of correct classifications of prematurity and small for gestational age than did estimates based on neurologic criteria or neurologic and physical criteria combined. These results support the use of physical criteria rather than neurologic or combined criteria for the clinical assessment of gestational age in low birth weight infants. In a subsample of 511 black and white infants, there were no ethnic differences in mean error of estimate for any of the three methods.

Abstract

This article reports the findings of a study designed to evaluate the long-term effectiveness of an industry-based relaxation training program in the treatment of hypertensives whose blood pressures were not well controlled by antihypertensive medication. Following a three-stage screening process, 137 participants were randomly allocated to either relaxation training (RT) or to blood pressure monitoring (BPM) at two worksites. Participants continued to receive medical care from their primary physicians during the course of the study. The advantage for participants receiving RT, in terms of mean blood pressure changes, was modest and of short duration. However, a larger proportion of participants in the RT group came into good control (blood pressures below 90 mm Hg) than in the BPM group following treatment (69.4% vs 41.5%, p less than 0.001). This advantage continued to 24 months' follow-up (63.9% vs 47.7%, p less than 0.05). At 30 months' follow-up there was no significant difference between the groups (75.0% vs 70.8%). Within-group analyses revealed that the BPM group also achieved significant blood pressure lowering which was maintained during the study. The largest initial difference between the two groups was for individuals whose entry diastolic blood pressures were most out of control despite several years of pharmacologic treatment. No difference was found between the two groups in the prescription of antihypertensive medication.

Abstract

Using data from the large number of adolescents studied in cycle III of the National Health Examination Survey, we utilized a sexual maturity index to develop a set of growth curves that reduce the distortion caused by commingling height data from adolescents maturing at different rates. We also created a set of correction tables to be used with these curves to permit the calculation of an adjusted height percentile that compensates for the effects of the differing rates of pubertal maturation. These adjusted height percentiles should remain more constant throughout puberty than height percentiles obtained from traditional growth curves; they may thus be used to estimate final adult height with only data obtained during routine physical examinations, by assuming that subjects maintain their adjusted height percentile through adolescence to adulthood. Height predictions made in this manner compare favorably with predictions made using two clinically tested algorithms.

Abstract

A prospective study of a cohort of healthy infants observed from birth to 2 years of age was carried out to investigate factors influencing the development of early adiposity. Infant suckling was measured in the laboratory twice during the first month of life. Multiple regression analyses revealed that parental educational level and a measure of feeding behavior, the interval between bursts of suckling, accounted for 18% of the variance in triceps skinfold measures at 1 year of age. A lower level of education and shorter interburst interval were associated with increased adiposity. Two feeding variables, pressure of suckling and the number of reported feeds per day, accounted for 21% of the variance in skinfold thickness at 2 years of age. Fewer, but larger, feeds and a higher sucking pressure were associated with a greater degree of adiposity. It seems that a vigorous infant feeding style, consisting of sucking more rapidly, at higher pressure, with a longer suck and burst duration, and a shorter interval between bursts of sucking, is associated with higher caloric intake and greater adiposity. The early development of this feeding style suggests that it may be a genetically endowed behavior. Breast-feeding protected against early adiposity only to the age of 6 months in this cohort of infants.

Abstract

This cross-sectional, multivariate study investigated associations between sleep disordered breathing (SDB) and putative risk factors in a heterogeneous group of 720 individuals over the age of 50 years studied during all-night in-lab polysomnography. Results indicated that: aged men were more likely to show impaired respiration during sleep than aged women; excessive daytime somnolence and parasomniac symptoms (snoring, gasping during sleep) were associated with SDB but insomnia was not; obesity accounted for more variance in SDB than age per se, implying that the prevalence of SDB in some elderly persons could be related to the deposition of body fat seen as individuals grow older. All four risk factors (age, sex, obesity, and symptomatic status) were statistically significant and independent predictors of impaired respiration in sleep in the elderly.

Abstract

Presented herein is a step-by-step discussion of the statistical evaluation of a medical test, using the literature concerning the DST to provide good and bad examples of its implementations. Specific topics of concern include: (1) conceptualization issues such as the definition of a test and its purpose; (2) implementation issues such as sampling and blindness; (3) analytic issues such as choice of statistical measures of quality; (4) issues of correct and realistic interpretation of results; and, finally (5) cost-benefit issues.

Abstract

A method is presented for empirical subclassification of autistic and autisticlike children, based on observations of current behavior. The advantage of the method is that it identifies profiles of co-occurring behaviors and accordingly assigns children to subtypes. The subtypes are more clinically homogeneous than the overall sample of autistic children. Preliminary findings are presented, including an effort to validate the subclasses by suggesting possible relationships between subtype membership and perinatal markers, developmental milestones, and independent measures of concurrent behavior.

Abstract

A portable solid-state recorder-display system was used to measure and analyze heart rate during the waking hours of 3 consecutive days in free-living sedentary normal middle-aged men who were randomized to undergo 3 regimens of physical activity during a 12-week period: low-intensity exercise training at home (n = 21), high-intensity exercise training at home (n = 23) and customary activity (n = 20). This was done to determine whether the system could detect changes in heart rate and, indirectly, in physical activity within the 3 groups. In both training groups the percentage of total recorded time spent within the prescribed high or low heart rate range recorded at 6 or 12 weeks increased significantly (p less than 0.05), whereas control subjects showed no increase above baseline values. Peak oxygen consumption increased by 8% and 17% in men undergoing low- and high-intensity training, whereas in control subjects it did not change. This solid-state system reliably measures prescribed increases in heart rate and provides an indirect measure of physical activity in normal sedentary men undergoing exercise training at home.

Abstract

Independence in daily life, family harmony as perceived by youths and their parents, and self-esteem were investigated in relation to anticonvulsant medication compliance in 25 epileptics aged 9-17 years. Medication compliance was assessed by monthly home saliva sampling for phenobarbital concentrations. Psychosocial issues were assessed by standardized instruments. Each psychosocial issue was highly correlated with compliance. Partial correlation analysis reveals that these findings are not explained by the subject's demographic or clinical characteristics. Medication noncompliance appears to be associated with a restriction of independence in daily life, lack of harmony in family relations, and low self-esteem in teenage epileptics. Clinicians should observe for these conditions and initiate patient and family counseling in order to maximize medication compliance and seizure control.

SLEEP-WAKE STATE ORGANIZATION, NEONATAL ASSESSMENT AND DEVELOPMENT IN PREMATURE-INFANTS DURING THE 1ST YEAR OF LIFE .2.SLEEPAnders, T. F., KEENER, M. A., Kraemer, H.1985; 8 (3): 193-206

Abstract

Twenty four premature infants were evaluated in their homes at seven ages during the first year of life to determine whether sleep-wake state organization was related to either neonatal assessment or short-term developmental outcome measures. A model assessing environmental and biological influences on the maturational course of selected sleep-wake state parameters was also evaluated. Sleep-wake state variables and neonatal assessment items were related to each other, and both predicted developmental quotients at 6 months and 1 year of age. Concordance was present primarily in the domain of motor activities. Waking motor behaviors and motor activity in sleep seem to independently reflect an infant's level of developmental organization. Individual sleep-wake state variables were influenced by both biological and environmental factors during maturation. The developmental course of quiet sleep is primarily biologically determined, as evidenced by its relationship to the infant's birth status (gestational age or birth weight); the infant's behavior that results in being taken from the crib during the night, and the course of his/her sleep that occurs between midnight and morning are dependent on both biological factors (perhaps infant irritability), and post-birth experiences (perhaps the caregiver's response to infant irritability). The course of active sleep and wakefulness are dependent solely on environmental influences, and not on maturity at birth.

Abstract

The prognostic value of symptom-limited treadmill exercise electrocardiography, exercise thallium myocardial perfusion scintigraphy and rest and exercise radionuclide ventriculography was compared in 117 men, aged 54 +/- 9 years, tested 3 weeks after a clinically uncomplicated acute myocardial infarction (MI). During a mean follow-up period of 11.6 months, 8 men experienced "hard" medical events (cardiac death, nonfatal ventricular fibrillation or recurrent MI) and 14 were hospitalized for unstable angina pectoris, congestive heart failure or coronary bypass surgery (total of 22 combined events). By multivariate analysis (Cox proportional hazards model), peak treadmill work load and the change in left ventricular ejection fraction (EF) during exercise were significant (p less than 0.01) predictors of hard medical events; these 2 risk factors and recurrent ischemic chest pain in the coronary care unit were also significantly predictive (p less than 0.001) for combined events. A peak treadmill work load of 4 METs or less or a decrease in EF of 5% or more below the value at rest during submaximal effort distinguished 22 high-risk patients (20% of the study population) from 89 low-risk patients. The rate of hard medical events within 12 months was 23% (5 of 22 patients), vs 2% (2 of 89 patients) in the high- and low-risk patient subsets, respectively (p less than 0.001). Thus, in patients who underwent evaluation 3 weeks after a clinically uncomplicated MI, exercise radionuclide ventriculography contributed independent prognostic information to that provided by symptom-limited treadmill testing and was superior to exercise thallium scintigraphy for this purpose.

Abstract

Previous methods for the analysis of temporal structure in sleep and other state time series have described cycles, rhythms, and semi-Markov chains. Methods, however, have been subjective and arbitrary. We propose an objective system of classification for these series, based on definitions of temporal structure which are consistent with those long used in the analysis of quantitative series. An ordered sequence of statistical tests is described which classifies observed behavioral state time series into four primary categories. The system is illustrated with examples from normal infant sleep. The results show that some infant sleep series are cycles, as previously reported, some are semi-Markov chains, and some are neither. The proposed objective methods promise consistency, clarity, and a richer understanding of behaviors such as sleep.

The treatment of anorexia nervosa: do different treatments have different outcomes?Research publications - Association for Research in Nervous and Mental DiseaseAgras, W. S., Kraemer, H. C.1984; 62: 193-207

Abstract

The probenecid-induced accumulation of the acidic metabolites of dopamine and serotonin is widely used to estimate the CNS turnover of these amines in human subjects. The theoretical basis of the probenecid test is discussed, including the assumptions on which the test is based, and the limitations of the procedure. Suggestions are offered on appropriate methods for analyzing test data. Available evidence suggests that maximal inhibition of the efflux of the acidic metabolites of dopamine and serotonin from the CSF is not achieved with probenecid doses up to 100 mg/kg. Therefore, before a comparison can be made between the accumulation of CSF metabolites from different groups of subjects, a correction for CSF probenecid concentrations is necessary. Moreover, in addition to the measurement of dopamine and serotonin turnover, the probenecid test can be extended to include comparisons of CNS turnover of other monoamines including octopamine, p-tyramine, and tryptamine.

Abstract

Longitudinal research suggests that characteristic levels of individual energy expenditure are enduring over time and influencing personality development. To measure characteristic levels of energy output at the very beginning of life, the activity and crying patterns of 72 normal neonates were monitored for 1-3 days by an electronic activity monitor. This monitor measures crying, noncrying, and total activity of various amplitudes and cry time. Day-to-day stability was highly significant in daytime crying, noncrying and crying activity, and median amplitude of noncrying movements. The amplitude of noncrying movements had the highest day-to-day stability, with correlations of .69-.80 This measure of the vigor of the infants' movements was not related to the infants' activity level as expressed in the frequency of movements and was not confounded by the infants' crying. The activity and crying measures were not significantly affected by the infants' sex or weight, length of labor, maternal parity, or by the analgesic drugs used during labor and delivery. Over the first 3 days of life, the amplitude or vigor of the infants' movements increased, while the frequency of motions did not change significantly.

Abstract

Chisholm et al. [4], using samples of Navajo and Malaysian newborns, found a significant positive relation between maternal normotensive blood pressures during the second trimester of pregnancy and at delivery and infant irritability in response to the Brazelton Examination. Measuring spontaneous crying with an electronic activity monitor and using a white middle-class American population, this relation was replicated for mothers with normotensive blood pressures during the third trimester of pregnancy. The combined findings of the 3 studies seem to suggest that maternal blood pressure in the latter part of pregnancy, even when within normal limits, is a factor in how irritable normal newborn infants are.

Abstract

A long-acting preparation of gonadotropin-releasing hormone (GnRH) was administered to three adult male chimpanzees living in a socially integrated group. Hormonal changes and behavioral responses were monitored for 8 days. Blood serum levels of luteinizing hormone peaked at about 8 hr and returned to baseline at 48 hr. Total serum testosterone reached the highest levels of 140% above baseline at 24 hr and returned to baseline after 48 hr. Out of a wide variety of behaviors observed in detail, only one cluster of three related behaviors showed even a suggestion of response: The two measures of activity, lone travel (p < 0.05) and distance traveled (p < 0.1), decreased on the day of hormone administration followed by an increase on the 2 subsequent days, and idle time (p < 0.1) revealed the reciprocal pattern. In view of various reports of behavioral effects of GnRH in other species, it is particularly noteworthly that parameters of sexual and agonistic behavior of male chimpanzees definitely did not change.

Abstract

To develop standards for distinguishing antiarrhythmic drug effect from spontaneous variability of premature ventricular complexes (PVCs), 21 males (mean age 56 +/- 8 years) with chronic ischemic heart disease and PVCs underwent symptom-limited treadmill exercise testing and 24-hour ambulatory monitoring before and after 2 weeks of placebo medication. Linear regression analysis was used to describe the relationship between baseline and placebo PVC frequency for various indexes of ventricular ectopic activity and to establish 95% and 99% one-tailed confidence intervals for this relationship within the group of 21 patients. The lower limit of baseline PVC frequency for which the procedure could distinguish a placebo from a true drug response, termed the "sensitivity threshold," was an average frequency of 2.2 PVCs/hour for ambulatory electrocardiographic monitoring and 1.2 PVCs/min for treadmill exercise testing. All patients exceeded the sensitivity threshold on baseline ambulatory ECGs, but only 38% of patients did so on baseline treadmill exercise tests. To establish antiarrhythmic efficacy with 95% confidence, the minimal percent reduction of PVCs between baseline and placebo visits was 68% for treadmill exercise testing and 65% for ambulatory electrocardiography. Although these standards were developed in patients with chronic ischemic heart disease, the model can be used to establish antiarrhythmic drug efficacy in any patient group.

Abstract

The authors report cerebrospinal fluid (CSF) concentrations of five monoamine metabolites before and after probenecid administration in normal subjects and patients with depression and schizophrenia. No differences were found in baseline metabolite concentrations among the three groups. CSF metabolite and CSF probenecid concentrations were significantly correlated in depressed patients for all metabolites, and there was decreased postprobenecid accumulation of homovanillic acid in the CSF of depressed patients compared with schizophrenic patients and with normal subjects. The authors propose a method for correcting for probenecid concentrations. Data from normal subjects should be of value for other investigators using the probenecid technique.

Abstract

In 3 groups of human newborns, 5 sex hormones were assayed from samples of umbilical-cord blood, and concentrations were analyzed by the sex and birth order of the infants. The 5 hormones assayed were testosterone, androstenedione, estrone, estradiol, and progesterone. Concentrations of testosterone were significantly greater in males than females. The other 4 hormones did not differ significantly by sex. In both sexes, firstborns had significantly more progesterone and estrogens, with progesterone showing the largest birth-order effects. Among male infants, firstborns had higher concentrations of testosterone. The higher concentrations of progesterone in firstborns of both sexes, and of testosterone in firstborn boys, were found not to be due to length of labor, birth weight, or maternal age. However, they were a function of temporal spacing of childbirths. Later borns who were closely spaced in relation to their next-older siblings had lower concentrations of hormones. The effect of temporal separation was greater on male than female infants for each of the 5 hormones studied. The results are discussed in terms of the possible effects of hormone "depletion" on the psychological development of closely spaced later borns.

Abstract

Gonadotropin-releasing hormone in doses up to 500 microgram was administered to 12 healthy male volunteers. Luteinizing hormone and testosterone levels increased subsequent to GnRH administration. No immediate effects of GnRH on mood and behavior were noted, though an increase in alertness, a decrease in anxiety and fatigue, and an increased speed of performance on automatized motor tasks were noted several hours after GnRH administration.

Abstract

Twenty males participated in a 2-month study examining the relationship between 8 a.m. plasma testosterone levels and orgasmic frequency. Within subjects, higher levels of testosterone are associated with periods of sexual activity. Over subjects, however, the direction of the relationship is reversed. Mean testosterone levels were higher for sexually less active individuals.

Abstract

In this study we identified consistent characteristics of the sleep-wake state of newborn infants. Forty-one normal, full-term infants were observed in a warmer-skin temperature maintained at 36.1 degree C--located in a sound-attenuated room for 1 hr during 2 successive mid-feeding periods. The infant's state was recorded on a check-list every 10 sec using the following categories for sleep and wakefulness: Quiet Sleep A, Quiet Sleep B, Active Sleep Without REM, Active Sleep With REM, Active Sleep With Dense REM, Drowsy, Alert Inactivity, WAKING Activity, Fussing, Crying, and Indefinite State. Immediately following the completion of each observation, the 2 observers made independent judgments of the degree of organization shown by the infant, using a 6-point scale. Over the two 1-hr observations, only Quiet Sleep A, Quiet Sleep B, and Crying showed any consistency. Active Sleep as typically defined showed no consistency whatsoever. However, 2 of the 3 components of Active Sleep were significantly reliability measures for the 2 observations; in sleeping infants all 3 components of active sleep showed high reliability. These results indicate that Active Sleep may be a composite of at least 3 meaningful categories. To look at overall state organization in the neonate, including both sleep and wake states, we considered Active Sleep as 3 separate states and then combined the resulting 11 behavioral states into derived clusters such that each combination of states showed a test-retest reliability above .52. With these 5 state clusters we viewed each infant's state behaviors in terms of a profile depicting the percent of time spent in each state cluster. We found a close association between these profiles and the subjective judgments of sleep-wake state organization made by the observers. The results clearly indicate that a 1-hr observation provides reliable information on individual sleep-wake states in the newborn.

Abstract

The object of the study was to assess the lability of testosterone levels in plasma of normal human males over a long period of time and to search for periodicities in changing levels. Blood samples obtained from 20 healthy young men every second day for 2 months were assayed for total testosterone concentration by radioligand saturation analysis with late-pregnancy plasma. The flucturations of plasma testosterone levels over the total time span were substantial for most individuals; the coefficients of variation ranged from 14 to 42% (median 21%). The presence of periodic functions in these fluctuations was tested by 4 different, relatively independent methods. Close agreement among at least 3 analytic methods was found for 12 out of the 20 subjects. These 12 subjects had cycles of plasma testosterone levels with periods ranging between 8-30 days, with a cluster of periods around 20-22 days. The majority of such cycles were significant at least at the 5% level. The mean amplitudes of these cycles ranged from 9 to 28% of the subjects' mean testosterone levels (average 17%).

Abstract

Two types of waterbeds were developed to impart compensatory vestibular-proprioceptive stimulation to premature infants. Twenty-one infants ranging in gestational age from 27 to 34 weeks and birthweights from 1,050 to 1,920 gm were included in this pilot study. Assignment to experimental and control groups was made by random design. The experimental group consisted of ten infants who were placed on a gently oscillating waterbed before the sixth postnatal day, where they remained for seven days. Their clinical progress was compared with that of a control group of 11 similar babies. Waterbed flotation was found to be a safe procedure; there was no significant effects on the infants' vital signs, weight, or frequency of emesis. Highly significant differences were found in the incidence of apnea between the two groups, with infants on the oscillating waterbed having significantly fewer apneic spells. Infants placed on the waterbed during the first four postnatal days benefited more than those placed later. A non-oscillating waterbed was found clinically useful for very small prematures with severe skin problems, for infants recovering from abdominal surgery, and for infants receiving parenteral nutrition.

Abstract

The association between mood and plasma testosterone was investigated. Every second day for 2 months, a Multiple Affect Adjective Checklist was filled out by 20 young men. Blood samples taken at the same time were analyzed for testosterone concentration. Relationships between hostility, anxiety, and depression and plasma testosterone levels were tested both within and across individuals. Intrasubject correlation coefficients between affects and hormone were fairly evenly distributed between positive and negative values, some significant on either side. Intersubject correlation coefficients were all positivie. Between depression and testosterone, the correlation was significant only at the 10% level; between the other two affects and testosterone, the correlations were not significant.